I. Organism Information

A. Taxonomy Information

1. Species:
   1. Powassan virus (Website 1):
      1. Ontology: UMLS:UMLS:C0032859
      2. GenBank Taxonomy No.: 11083
      3. Description: Powassan virus (POWV) circulates in South Dakota, the Eastern and Western United States, Canada, and Far Eastern Russia and is readily differentiated from the other tick-transmitted virus species by serologic tests. It was first isolated in 1958 from the brain of a 5-year old boy who died from encephalitis in Powassan, Ontario, Canada. In North America, POWV causes severe encephalitis in humans with a high incidence of neurologic sequelae and up to 60% case-fatality rate (Gritsun et al., 2003). Powassan virus is a flavivirus and a member of the tick-borne encephalitis (TBE) antigenic complex (Kuno et al., 2001).
      4. Variant(s):
         • Tick-borne powassan virus (strain lb) (Website 2):
           • GenBank Taxonomy No.: 39008
           • Parent: Powassan virus
           • Description: The LB strain was isolated in 1958 in Ontario, Canada from a human brain (Kuno et al., 2001). Shestopalova et al. undertook a comparative electron microscopic study of two POW strains: the prototype LB strain from Canada and strain AN-750 isolated from a pool of An. hyrcanus collected in the USSR. They studied virus in the cerebral and cerebellar cortex of newborn and adult white mice that had been inoculated I.S. Both strains exhibited identical morphological characteristics by electron microscopy (Artsob, 1989).

B. Lifecycle Information :

1. Description: In North America, the virus is transmitted in a cycle involving small mammals (principally squirrels and ground hogs) and Ixodes species ticks, including Ixodes marxi and Ixodes cookei in the east, and Ixodes spinipalpis in the west (Burke and Monath, 2001).

C. Genome Summary:

1. Genome of Powassan virus
1. Description: The genome RNA of flaviviruses is single-stranded and approximately 11 kilobases in length. The genomic RNA is infectious, and thus of positive polarity encoding the viral proteins necessary for RNA replication. Genome-length RNAs appear to be the only virus-specific mRNA molecules in flavivirus-infected cells (Chambers et al., 1990).
2. Single RNA strand (Website 3):
   1. GenBank Accession Number: NC_003687
   2. Size: 10839 bp ss-RNA (Website 3)
   3. Gene Count: The genome of POW virus is 10839 nucleotides long and contains a single long open reading frame which codes for a 3415 amino acid-long polyprotein (Mandl et al., 1993).
   4. Description: The genome of POW virus is 10839 nucleotides long and contains a single long open reading frame which codes for a 3415 amino acid-long polyprotein. The computer analysis of this protein sequence and its comparison with TBE virus revealed the presence of homologous potential protease cleavage sites, internal signal sequences, stop transfer, and transmembrane sequences, suggesting that the POW virus polyprotein is co- and post-translationally cleaved into the mature viral protein (structural proteins C, (pr) M, and E; nonstructural proteins NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5) in the same manner as other flaviviruses (Mandl et al., 1993).
   5. Picture(s):
      1. Powassan virus (Website 4):
         
         
         
         Description: Powassan virus, complete genome (Website 4)
         

II. Epidemiology Information

Powassan virus infection appears to be one of the least common causes of arbovirus encephalitis reported in cases from the United States and Canada, ranking behind LaCrosse, St. Louis and eastern and western equine encephalitis. However, Powassan virus and eastern equine encephalitis have the dubious distinction of having the highest case-fatality rates and are associated with a very high incidence of neurologic sequelae. Humans are accidental victims when they enter into areas where the virus, the arthropod vector (an ixodid tick) and the vertebrate natural hosts coexist. Among the most commonly implicated natural hosts are the woodchuck and snowshoe hare. However, other animals that humans come into contact with including coyotes, foxes, raccoons and skunks have shown serological evidence of infection. Moreover, the scope of transmission of the virus may be broadened by domestic cats and dogs, which can act as harbingers of infected ticks and thereby expose humans. Cases of arbovirus encephalitis have been reported from Ontario, Quebec and New Brunswick in Canada and from New York, Pennsylvania and Massachusetts in the United States. Surveillance serologic studies have been positive in up to 3% of the population in certain northern Ontario communities, suggesting that infection without encephalitis can occur in humans (Ralph, 1999).

A. Outbreak Locations:

1. During September 1999 - July 2001, four Maine and Vermont residents with encephalitis were found to be infected with POW virus (MMWR, 2001).

B. Transmission Information:

1. From: Vertebrate (at lifecycle stage: Vertebrate), To: Invertebrate (at lifecycle stage: Invertebrate) , With Destination: Invertebrate (at lifecycle stage: Invertebrate)
   Mechanism: Infected deer ticks (Ixodes scapularis) were allowed to attach to naive mice for variable lengths of time to determine the duration of tick attachment required for Powassan (POW) virus transmission to occur. Viral load in engorged larvae detaching from viremic mice and in resulting nymphs was also monitored. Ninety percent of larval ticks acquired POW virus from mice that had been intraperitoneally inoculated with 10(5) plaque-forming units (PFU). Engorged larvae contained approximately 10 PFU. Transstadial transmission efficiency was 22%, resulting in approximately 20% infection in nymphs that had fed as larvae on viremic mice. Titer increased approximately 100-fold during molting. Nymphal deer ticks efficiently transmitted POW virus to naive mice after as few as 15 minutes of attachment, suggesting that unlike Borrelia burgdorferi, Babesia microti, and Anaplasma phagocytophilum, no grace period exists between tick attachment and POW virus transmission (Ebel et al., 2004).
   
   
2. From: Invertebrate (at lifecycle stage: Invertebrate), To: Vertebrate (at lifecycle stage: Vertebrate) , With Destination: Mammals (at lifecycle stage: Vertebrate)
   Mechanism: Infectious POW virus is present in tick salivary secretions inoculated during the earliest stages of feeding, and may be immediately inoculated (Ebel et al., 2004). D. andersoni were fed on viremic New Zealand white rabbits and POW virus multiplication demonstrated in various tick organs including salivary glands, Gene's organ glands, and accessory glands. POW virus was transmitted to rabbits, hamsters, and guinea pigs by the bites of infected ticks (Artsob, 1989).
   
   
3. From: Vertebrate (at lifecycle stage: Vertebrate), To: Vertebrate (at lifecycle stage: Vertebrate) , With Destination: Vertebrate (at lifecycle stage: Vertebrate)
   Mechanism: A lactating goat with a 74-day-old kid was inoculated with 10(3) mouse 50% lethal dose (LD50) of Powassan virus. No ensuing viremia could be detected, but virus was secreted in the milk on postinoculation days 7 through 15, with a titer of 10(5) LD50/ml on day 12. Neutralizing antibody was found in the serum on days 22 through 36 and in the milk on day 36. The offspring was not inoculated but was allowed to continue feeding on its mother's milk. It developed neutralizing antibody by day 22. Since the kid was past the age when it could resorb antibody from the milk, its serum antibody was evidence of active infection. Neither animal showed any clinical sign of illness. A serum survey of 499 goats in New York State showed that 9 had neutralizing antibodies to Powassan virus. These immune goats came from widely scattered localities, including counties where human cases have been confirmed. The findings suggest the possibility of milk-borne transmission of Powassan virus from goat to man (Woodall and Roz, 1977).
   
   

C. Environmental Reservoir:

1. Mammals :
   1. Description: Neutralizing antibodies to Powassan virus have been found in numerous small mammals. Powassan virus has been isolated from marxi ticks collected from one red squirrel, T. hudsonicus, and from the blood of another squirrel. Isolations of Powassan virus, as well as high antibody prevalence in squirrels and ground hogs in the North Bay-Powassan region of Ontario, have led to the consideration of these animals as important reservoirs in the maintenance cycle of Powassan virus (Calisher, 1994). The catholic host preference of POW vectors ensures that many vertebrates in endemic areas likely to encounter virus infection, including domestic animals. The viremia in many POW infected vertebrates has tended to be relatively low, i.e. 10(2.5) LD(50) or less. However, the long feeding periods of most ticks and their enormous meals may allow sufficient virus intake to infect ticks. Thus, numerous mammals, primarily of the orders Rodentia and Carnivora, likely can contribute to the POW amplification cycle. Vertebrate behavioral patterns, including the nesting and social interaction of potential reservoir hosts, are important contributing factors to the probability of animals serving as tick hosts. The use of a single den by several individuals, such as a female woodchuck and her offspring or males seeking females, provides opportunities for exchanges of POW-infected ticks. The population dynamics of the vertebrate hosts are of relevance. Many of the Rodentia and Carnivora that serve as reservoir hosts of POW virus have brief life spans (usually less than 2 or 3 years) and high reproductive rates (two to ten progeny per year). Thus, many new susceptibles are introduced into the population each year ensuring the ready availability of POW amplifying hosts in endemic areas (Artsob, 1989). Main presented the following three postulated enzootic cycles for POW virus in North America: 1. Arboreal squirrels and Ix. marxi in the East. 2. Medium-sized rodents and carnivores and Ix. cookei in the East and the Midwest. 3. Small and medium-sized mammals and Ix. spinipalpus in the Northwest (Artsob, 1989).

D. Intentional Releases:

1. Intentional Release information :
   1. Description: Tick-borne flaviviruses are excreted in the urine and feces of experimentally infected animals but it is unlikely that this form of virus would provide an efficient route of infection for humans. Perhaps their greatest weakness as biological weapons is the fact that they are normally transmitted to vertebrate hosts via the bite of an infected tick, and the natural habitat of ticks is the forest or moist thick grassy vegetation as found on uplands. Under most circumstances this means that humans and even most animals would be a dead-end for virus transmission because few humans are exposed to the bite of a tick. Another important factor is that these viruses are all antigenically closely related. Therefore, immunity against one strain is likely to produce cross-immunity against the others. Moreover, in endemic regions there is a reasonably high level of immunity amongst the indigenous viruses. One can ask the question whether or not it is feasible to spread the virus by infecting large numbers of ticks with the virus. This would not be a logical approach for the following reasons: (a) very large numbers of infected ticks would be required and logistically this would be technically extremely difficult; (b) ticks only feed three times, at very critical stages of their life cycle and it would be extremely difficult to arrange for them to be infected and ready to feed when delivered as weapons; (c) the production of a sufficiently large number of ticks to pose a threat to human or animal populations would also be a difficult technical exercise. In summary, these viruses are unlikely to be the most effective front line weapons in biological warfare but they might be capable of causing significant problems on a small scale (Gritsun et al., 2003b).
   2. Delivery mechanism: In the context of bioterrorism, we have shown that the tick-borne flaviviruses are pathogenic for humans and some animals. Some strains are more virulent than others but even the most virulent viruses are unlikely to produce high fatality rates. These viruses can infect via the alimentary tract and also when inoculated intranasally into experimental animals. Presumably, therefore concentrated aerosols would be infectious or high virus concentrations delivered as a powder contaminating food might infect a significant proportion of people eating the food (Gritsun et al., 2003b). One can ask the question whether or not it is feasible to spread the virus by infecting large numbers of ticks with the virus. This would not be a logical approach for the following reasons: (a) very large numbers of infected ticks would be required and logistically this would be technically extremely difficult; (b) ticks only feed three times, at very critical stages of their life cycle and it would be extremely difficult to arrange for them to be infected and ready to feed when delivered as weapons; (c) the production of a sufficiently large number of ticks to pose a threat to human or animal populations would also be a difficult technical exercise (Gritsun et al., 2003b).

III. Infected Hosts

1. Human:
   1. Taxonomy Information:
      1. Species:
         1. Human (Website 50):
            • Ontology: UMLS:C0086418
            • GenBank Taxonomy No.: 9606
            • Scientific Name: Homo sapiens (Website 50)
            • Description: The disease occurs in Russia, Canada, and the United States. In North America, Powassan encephalitis has been reported in Ontario, New York, and Pennsylvania, with a total of 20 cases, 18 in people younger than 20 years of age, and one death. Most cases have been in males, probably reflecting increased outdoor activity and exposure to ticks. Human infections are rare; antibody surveys in the United States and Canada have generally shown prevalence rates of 0.5% to 4%. The virus has a much wider geographic distribution than indicated by case reports, and Powassan infection should therefore be suspected in cases of encephalitis throughout the United States and Canada (Burke and Monath, 2001).
      
      
   2. Infection Process:
      1. Infectious Dose: The prevalence of exposure to POW virus among human residents of deer tick-infested areas, and the relationship between viral inoculum and POW viral pathogenesis remains poorly described. It may be that a large viral inoculum, delivered over several hours or days, is required to produce illness in humans (Ebel et al., 2004).
      2. Description:
      
      
   3. Disease Information:
      1. Powassan Encephalitis :
         1. Pathogenesis Mechanism: Because so few cases of clinically apparent POW virus infection have been recorded, few definitive and generally applicable statements can be made about infection with this virus. In the few human infections described, onset is sudden, with headache and fever to 40 C and convulsions. Prodromal symptoms include sore throat, sleepiness, headache, and disorientation. Encephalitic cases are characterized by vomiting, prolonged fever or fever of variable length, respiratory distress, lethargy, and other nonspecific symptoms throughout the acute phase. Patients may become semicomatose with some paralytic manifestations, but general neurologic signs of meningeal irritation presage encephalitis, which is often severe. Most diagnosed cases display evidence of focal lesions, but one patient had major involvement of the right temporal lobe, more typical of herpes encephalitis (Calisher, 1994). Russian workers, analyzing 14 cases of POW encephalitis, reported seven patients (one death) with signs of meningoencephalitic lesions, two with meningeal manifestations, and five with unapparent or uncomplicated febrile infections. POW encephalitis was characterized by signs of cerebellovestibular lesions, which differ from signs of tick-borne encephalitis (Calisher, 1994). Patients may become semicomatose with some paralytic manifestations, but general neurologic signs of meningeal irritation presage encephalitis, which is often severe (Calisher, 1994).
         
         
         
         2. Incubation Period: The incubation period is at least one week after being fed on by an infected tick (Calisher, 1994). The reported incubation periods for Powassan virus range from 8 to 34 days (Gholam et al., 1999).
         
         
         
         3. Prognosis: POW encephalitis is associated with significant long-term morbidity and has a case-fatality rate of 10% to 15% (MMWR, 2001). In Canada and the USA, POWV causes severe encephalitis in humans with a high incidence of neurological sequelae and up to 60% case fatality rate. In Far Eastern Russia POWV infections were described as milder than those produced by TBEV (tick-borne encephalitis virus) (Gritsun et al., 2003b). Over half (11/20) of the patients who survived had sequelae, and this rate may actually be higher because follow-up information was not available in some cases (Gholam et al., 1999).
         
         
         
         4. Symptom Information :
            • Syndrome -- Powassan Encephalitis:
              • Description: Powassan encephalitis is the name applied to the human disease. Clinical disease has not been demonstrated in lower animals infected with Powassan virus in nature (Artsob, 1981).
              • Observed: Twenty-seven symptomatic cases of Powassan virus encephalitis have been reported in North America between 1958 and 1998; 23 are published, and 4 are unpublished. Of note, 11 of the 23 cases were acquired in Canada, 7 of those in Ontario, and the majority (10/12) of cases reported in the United States originated in New York state (Gholam et al., 1999).
              
              
              Symptoms Shown in the Syndrome:
              
              
              • Sore throat:
                • Ontology: UMLS:C0242429
                • Description: Sore throat (Gholam et al., 1999) Prodromal symptoms include sore throat, sleepiness, headache, and disorientation (Calisher, 1994).
              • Sleepiness:
                • Ontology: UMLS:C0013144
                • Description: Sleepiness (Gholam et al., 1999) Prodromal symptoms include sore throat, sleepiness, headache, and disorientation (Calisher, 1994).
              • Headache:
                • Ontology: UMLS:C0018681
                • Description: Headache (Gholam et al., 1999) In the few human infections described, onset is sudden, with headache and fever to 40 C and convulsions (Calisher, 1994).
              • Disorientation:
                • Ontology: UMLS:C0233407
                • Description: Disorientation (Gholam et al., 1999) Prodromal symptoms include sore throat, sleepiness, headache, and disorientation (Calisher, 1994).
              • Vomiting:
                • Ontology: UMLS:C0042963
                • Description: Vomiting (Gholam et al., 1999) Encephalitic cases are characterized by vomiting, prolonged fever or fever of variable length, respiratory distress, lethargy, and other nonspecific symptoms throughout the acute phase (Calisher, 1994).
              • Respiratory distress:
                • Ontology: UMLS:C0476273
                • Description: Respiratory distress (Gholam et al., 1999) Encephalitic cases are characterized by vomiting, prolonged fever or fever of variable length, respiratory distress, lethargy, and other nonspecific symptoms throughout the acute phase (Calisher, 1994).
              • Convulsions:
                • Ontology: UMLS:C0009951
                • Description: Convulsions (Gholam et al., 1999) In the few human infections described, onset is sudden, with headache and fever to 40 C and convulsions (Calisher, 1994).
              • Fever:
                • Ontology: UMLS:C0015967
                • Description: Fever (Gholam et al., 1999) In the few human infections described, onset is sudden, with headache and fever to 40 C and convulsions (Calisher, 1994). Encephalitic cases are characterized by vomiting, prolonged fever or fever of variable length, respiratory distress, lethargy, and other nonspecific symptoms throughout the acute phase (Calisher, 1994).
              • Hemiplegia:
                • Ontology: UMLS:C0018991
                • Description: Hemiplegia (Gholam et al., 1999) The most common indication of neurologic damage was hemiplegia, but recurrent severe headaches and damage to the upper cervical cord resulting in paralysis and atrophy of shoulder muscles, a common feature of Russian spring-summer and Central European encephalitides, also have been reported (Calisher, 1994).
              • Minor memory impairment:
                • Ontology: UMLS:C0233794
                • Description: Minor memory impairment (Gholam et al., 1999) Recurrent severe headaches, minor memory impairment, and damage to the upper cervical cord resulting in paralysis and the wasting of right shoulder muscles were also reported (Gholam et al., 1999).
              • Paralysis:
                • Ontology: UMLS:C0522224
                • Description: Paralysis and wasting of right shoulder muscles (Gholam et al., 1999) The most common indication of neurologic damage was hemiplegia, but recurrent severe headaches and damage to the upper cervical cord resulting in paralysis and atrophy of shoulder muscles, a common feature of Russian spring-summer and Central European encephalitides, also have been reported (Calisher, 1994).
              • Lethargy:
                • Ontology: UMLS:C0023380
                • Description: Lethargy (Calisher, 1994) Encephalitic cases are characterized by vomiting, prolonged fever or fever of variable length, respiratory distress, lethargy, and other nonspecific symptoms throughout the acute phase (Calisher, 1994).
              • Hypotonia:
                • Ontology: UMLS:C0026827
                • Description: Hypotonia (Calisher, 1994) Neuromuscular manifestations, specifically hypotonia, have been documented in a middle-aged male patient from Ontario, Canada (Calisher, 1994)
              • Spasticity:
                • Ontology: UMLS:C0026838
                • Description: Spasticity (Calisher, 1994) Spasticity can persist for weeks after the initial illness in patients who eventually improve (Calisher, 1994).
              • Ophthalmoplegia:
                • Ontology: UMLS:C0026838
                • Description: Ophthalmoplegia (Lessell and Collins, 2003) Powassan infection was diagnosed from serum drawn 19 days after onset that was positive for Powassan-specific IgM and a neutralizing antibody titer of 1:640. PCR testing is not a requisite for diagnosis. Over the succeeding months, all nonocular signs improved. Seven months after onset, she had normal visual acuity, color vision, visual fields, lids, pupils, anterior segments, vitreous, and fundi. The right eye was slightly exotropic. She appeared unable to execute any eye movements on command, look to an eccentric target, or follow a target. However, with prolonged effort, after a 10- to 20-second delay, both eyes would drift conjugately 30 up or down and 20 left or right. The eyes would return slowly to the primary position. Doll's eye maneuvers elicited nearly full, but slow and delayed, conjugate excursions. Three months later, she could promptly initiate up-gaze, but the movements remained slow. No improvement occurred thereafter (Lessell and Collins, 2003).
         
         
         5. Treatment Information:
            • Symptomatic: Treatment is symptomatic (Burke and Monath, 2001).
              • Applicable: ()
      
      
   4. Prevention:
      1. Tick Avoidance and Control:
         • Ontology: UMLS:C0031249
         • Description: Because there is no vaccine or specific therapy for POW encephalitis, the best means of prevention is protection from tick bite. This includes using insect repellents, wearing light-colored clothing with long sleeves and pants tucked into socks or boots, avoiding or clearing brushy areas, and removing ticks before they attach or as soon after attachment as possible. Checking family pets also can prevent ticks from entering the home. Because Ix. cookei are often found on woodchucks and skunks and may be the primary vector of POW virus, environmental controls reducing human contact with small and medium-sized mammals should reduce risk for exposure to POW virus-infected ticks. Persons should keep areas adjacent to their home clear of brush, weeds, trash, and other elements that could support small and medium-sized mammals. When removing rodent nests, avoid direct contact with nesting materials and use sealed plastic bags for disposal to prevent direct contact with ticks (MMWR, 2001). There is currently no vaccine available for Powassan virus. Education is the best possible defense; people should be aware of tick-borne diseases and learn to avoid any contact with suspected vectors. Human protection is mainly achieved through wearing adequate clothing to minimize exposed skin, treating clothes with insecticides and avoiding or clearing brushy areas. The use of tick repellents and insecticides should be encouraged, and an effort should be made to control ticks in domestic and farm animals and in buildings that they frequent (Gholam et al., 1999).
      2. Pasteurize milk:
         • Ontology: UMLS:C0597885
         • Description: Woodall and Roz demonstrated the possibility of POW virus transmission through goat's milk. Thus, avoidance of unpasteurized milk is desirable (Artsob, 1981).
      
      
   5. Model System:
      1. Mouse:
         1. Ontology: UMLS:C0025914
         2. Model Host: Vertebrate. Mus musculus (Khozinskaia and Pogodina, 1982)
         3. Model Pathogens:
            • Powassan virus . Powassan virus (Khozinskaia and Pogodina, 1982)
         4. Description: Simultaneous inoculation of mice with tick-borne and Powassan viruses was shown, depending on experimental conditions, to result either in stimulation of infection or its unchanged course as compared with monoinfection and inoculation with the viruses at 2--3-week intervals in cross protection of mice against the superinfecting virus. Simultaneous inoculation of mice with the two viruses was accompanied by their multiplication in the blood and brains of mice and formation of antihemagglutinating antibodies to each of them. In the virus population in the brains of mice there was either formation of a mixture of two viruses or their phenotypic mixing. In cross protection, multiplication of the superinfecting virus in the blood and brain of mice was slightly inhibited, the antihemagglutinating antibody to a second virus either did not form or appeared in low titers (Khozinskaia and Pogodina, 1982).
      2. Rhesus:
         1. Ontology: UMLS:C0024400
         2. Model Host: Vertebrate. Macaca mulatta, Rhesus monkey (Frolova et al., 1985)
         3. Model Pathogens:
            • Powassan virus . Powassan virus (Frolova et al., 1985)
         4. Description: We have carried out a comparative study of the experimental infection of monkeys with the P-40 strain of the Powassan virus, isolated in the Primor'e Territory of the USSR, and with the Canadian prototype LB strain. The Powassan virus was found to be pathogenic for Macaca rhesus. The clinical and pathomorphological picture of the experimental encephalitis was studied, and the full identity of the infection produced in the monkeys by the P-40 strain and the Canadian LB strain of the Powassan virus was demonstrated. On electron microscopic examination of the central nervous system the virus was detected in the neurons, glial cells, and intercellular spaces. The virions of the strains studied have identical morphological parameters, being 37-45 nm in diameter and of spherical shape. The data obtained indicated a marked neurotropism of the virus. They will contribute to the elucidation of the role of the virus in the infection pathology of humans, i.e., in the differentiation of encephalitis cases not associated etiologically with the virus of the spring-summer tickborne encephalitis (Frolova et al., 1985).
      3. Rabbit:
         1. Ontology: UMLS:C0034493
         2. Model Host: Vertebrate. Oryctolagus cuniculus, rabbit (Little et al., 1985)
         3. Model Pathogens:
            • Powassan virus . Powassan virus strain M794 (Little et al., 1985)
         4. Description: Powassan virus strain M794, a member of the Flavivirus genus known to infect man and animals in Canada, was inoculated intracerebrally into rabbits and horses. No clinical signs were observed in rabbits, but widespread encephalitis resulted, characterized by lymphoid perivascular cuffing, lymphocytic meningitis, and lymphocytic choroiditis (Little et al., 1985). The virus could not be re-isolated from the rabbit or horse brains (Little et al., 1985).
      4. Horse:
         1. Ontology: UMLS:C0019944
         2. Model Host: Vertebrate. Equus caballus (Little et al., 1985)
         3. Model Pathogens:
            • Powassan virus . Powassan virus strain M794 (Little et al., 1985)
         4. Description: Powassan virus strain M794, a member of the Flavivirus genus known to infect man and animals in Canada, was inoculated intracerebrally into rabbits and horses (Little et al., 1985). In horses, eight days after inoculation, prominent neurological signs occurred and lesions were those of non-suppurative encephalomyelitis, neuronal necrosis, and focal parenchymal necrosis. The virus could not be re-isolated from the rabbit or horse brains (Little et al., 1985).
      5. Hamster:
         1. Ontology: UMLS:C0018557
         2. Model Host: Vertebrate. Cricetinae (Costero and Grayson, 1996)
         3. Model Pathogens:
            • Powassan virus . Powassan virus (Costero and Grayson, 1996)
         4. Description: Transmission experiments were performed with Ixodes scapularis ticks from an uninfected laboratory colony. Immature and adult ticks were exposed to Powassan (POW) viremic hamsters and rabbits, respectively. Oral infection rates for engorged larvae, nymphs and females fed on POW-infected hosts were 10%, 40%, and 57%, respectively. Transstadial transmission rates for nymphs exposed to POW virus as larvae, adults exposed as larvae, and adults exposed as nymphs, were 9.5%, 10%, and 54%, respectively. Evidence of transovarial transmission occurred when two uninfected hamsters, exposed to F2 larvae and nymphs originally exposed to POW virus in the F1 nymphal stage, seroconverted to POW virus with hemagglutination inhibition titers of 80 and 5,120, respectively; the transovarial transmission rate was 16.6% (Costero and Grayson, 1996).
      6. Goat:
         1. Ontology: UMLS:C1265550
         2. Model Host: Vertebrate. Capra hircus (Gritsun et al., 2003)
         3. Model Pathogens:
            • Powassan virus . Powassan virus (Gritsun et al., 2003)
         4. Description: Latent infection and milk-borne transmission of POWV in goats has been demonstrated experimentally (Gritsun et al., 2003).
2. Invertebrate:
   1. Taxonomy Information:
      1. Species:
         1. Dermacentor andersoni (Website 5):
            • Ontology: UMLS:C0323431
            • GenBank Taxonomy No.: 34620
            • Scientific Name: Dermacentor andersoni (Website 5)
            • Description: POW virus has been isolated from four species in North America ticks including Ixodes cookei (22 reported isolates), Ix. marxi (1 isolate), Ix. spinipalpis (1 isolate), and D. andersoni (2 isolates) (Artsob, 1989).
         2. Dermacentor silvarum (Gritsun et al., 2003b):
            • Ontology: UMLS:C0323435
            • GenBank Taxonomy No.:
            • Scientific Name: Dermacentor silvarum (Gritsun et al., 2003b)
            • Description: In Russia, POWV has been isolated from other tick species, namely I. persulcatus, H. neumanni, H. consinna and D. silvarum and replication in different tick species is believed to be a selection factor for different POWV strains (Gritsun et al., 2003b). In the environment POWV was isolated mainly from D. silvarum possibly because these ticks have a shorter life cycle feeding twice annually as larvae and nymphs, giving them a potential advantage for virus transmission (Gritsun et al., 2003).
         3. Dermacentor variabilis (Website 6):
            • Ontology: UMLS:C0011596
            • GenBank Taxonomy No.: 34621
            • Scientific Name: Dermacentor variabilis (Website 6)
            • Description: In Canada, POWV has been isolated from Ixodes cookei that feeds mainly on groundhogs (Marmota monax), Ixodes augustus which often bite humans and cats and Ixodes scapularis and Dermacentor variabilis which frequently bite humans and dogs (Gritsun et al., 2003b).
         4. Ixodes angustus (Website 7):
            • Ontology: UMLS:C1005681
            • GenBank Taxonomy No.: 35564
            • Scientific Name: Ixodes angustus (Website 7)
            • Description: In Canada, POWV has been isolated from Ixodes cookei that feeds mainly on groundhogs (Marmota monax), Ixodes augustus which often bite humans and cats and Ixodes scapularis and Dermacentor variabilis which frequently bite humans and dogs (Gritsun et al., 2003b).
         5. Ixodes cookei (Website 9):
            • Ontology: UMLS:C0323411
            • GenBank Taxonomy No.: 35565
            • Scientific Name: Ixodes cookei (Website 9)
            • Description: In Canada, POWV has been isolated from Ixodes cookei that feeds mainly on groundhogs (Marmota monax), Ixodes augustus which often bite humans and cats and Ixodes scapularis and Dermacentor variabilis which frequently bite humans and dogs (Gritsun et al., 2003b).
         6. Ixodes marxi (Artsob, 1989):
            • Ontology: UMLS:C0323402
            • GenBank Taxonomy No.:
            • Scientific Name: Ixodes marxi (Artsob, 1989)
            • Description: POW virus has been isolated from four species in North America ticks including Ixodes cookei (22 reported isolates), Ix. marxi (1 isolate), Ix. spinipalpis (1 isolate), and D. andersoni (2 isolates) (Artsob, 1989).
         7. Taiga tick (Website 8):
            • Ontology: UMLS:C0323406
            • GenBank Taxonomy No.: 34615
            • Scientific Name: Ixodes persulcatus (Website 8)
            • Description: In Russia, POWV has been isolated from other tick species, namely I. persulcatus, H. neumanni, H. consinna and D. silvarum and replication in different tick species is believed to be a selection factor for different POWV strains (Gritsun et al., 2003b).
         8. Black-legged tick (Website 10):
            • Ontology: UMLS:C0282510
            • GenBank Taxonomy No.: 6945
            • Scientific Name: Ixodes scapularis (Website 10)
            • Description: Powassan (POW) virus (Flaviviridae, Flavivirus) strains belonging to Lineage II (also referred to as tick virus), appear to circulate in nature in an enzootic cycle with deer ticks (Ixodes scapularis) serving as the main vector (Ebel et al., 2004). In Canada, POWV has been isolated from Ixodes cookei that feeds mainly on groundhogs (Marmota monax), Ixodes augustus which often bite humans and cats and Ixodes scapularis and Dermacentor variabilis which frequently bite humans and dogs (Gritsun et al., 2003b).
         9. Ixodes spinipalpis (Website 11):
            • Ontology: UMLS:C0323403
            • GenBank Taxonomy No.: 34614
            • Scientific Name: Ixodes spinipalpis (Website 11)
            • Description: POW virus has been isolated from four species in North America ticks including Ixodes cookei (22 reported isolates), Ix. marxi (1 isolate), Ix. spinipalpis (1 isolate), and D. andersoni (2 isolates) (Artsob, 1989).
         10. Haemaphysalis spp. (Website 14):
             • Ontology: UMLS:C0323443
             • GenBank Taxonomy No.: 34622
             • Scientific Name: Haemaphysalis spp (Website 14).
             • Description: In Russia, POWV has been isolated from other tick species, namely Ixodes persulcatus, Haemaphysalis neumanni, H. consinna and Dermacentor silvarum and replication in different tick species is believed to be a selection factor for different POWV strains (Gritsun et al., 2003b).
         11. Ochlerotatus togoi, Aedes togoi (Website 12):
             • Ontology: UMLS:C0322847
             • GenBank Taxonomy No.: 55967
             • Scientific Name: Ochlerotatus togoi, Aedes togoi (Website 12)
             • Description: Phylogenetic analysis shows that POWV emerged as the most ancestral lineage of the mammalian tick-borne viruses. Interestingly, the virus has also been isolated from mosquitoes, Anopheles hyrcanus and Aedes togoi (Gritsun et al., 2003).
         12. Anopheles hyrcanus (Website 13):
             • Ontology: UMLS:C0322930
             • GenBank Taxonomy No.: 138534
             • Scientific Name: Anopheles hyrcanus (Website 13)
             • Description: Phylogenetic analysis shows that POWV emerged as the most ancestral lineage of the mammalian tick-borne viruses. Interestingly, the virus has also been isolated from mosquitoes, Anopheles hyrcanus and Aedes togoi (Gritsun et al., 2003).
      
      
   2. Infection Process:
      
      No infection process information is currently available here.
      
      
   3. Disease Information:
      
      No disease information is currently available here.
      
      
   4. Prevention:
      
      No prevention information is currently available here.
      
      
   5. Model System:
      
      No model system information is currently available here.
      
      
3. Vertebrate:
   1. Taxonomy Information:
      1. Species:
         1. Ammospermophilus (Website 54):
            • Ontology: UMLS:C0324902
            • GenBank Taxonomy No.: 45485
            • Scientific Name: Ammospermophilus (Website 54)
            • Description: 24 out of 214 Ammospermophilus nelsoni were found to have antibodies to Powassan virus by hemagglutination-inhibition assays (Hardy et al., 1974).
         2. Heermann's kangaroo rat (Website 15):
            • Ontology: UMLS:C1095848
            • GenBank Taxonomy No.: 10018
            • Scientific Name: Dipodomys heermanni (Website 15)
            • Description: 13 of 88 Dipodomys heermanni were found to have antibodies to Powassan virus by hemagglutination-inhibition assays (Hardy et al., 1974).
         3. Kangaroo rat (Website 55):
            • Ontology: UMLS:C0012570
            • GenBank Taxonomy No.: 10016
            • Scientific Name: Dipodomys nitratoides (Website 55)
            • Description: 37 of 1,004 Dipodomys nitratoides were found to have antibodies to Powassan virus by hemagglutination-inhibition assays (Hardy et al., 1974).
         4. North American porcupine (Website 16):
            • Ontology: UMLS:C1005328
            • GenBank Taxonomy No.: 34844
            • Scientific Name: Erethizon dorsatum (Website 16)
            • Description: Other Rodentia from which POW isolates and/or neutralizing antibodies have been obtained include Columbian ground squirrel, golden mantled ground squirrel, Richardson's ground squirrel, porcupine, chipmunk, meadow mouse, woodland jumping mouse, deer mouse, gray squirrel, eastern chipmunk, and red squirrel (Artsob, 1989).
         5. Yellow-pine chipmunk (Website 17):
            • Ontology: UMLS:C1024864
            • GenBank Taxonomy No.: 64679
            • Scientific Name: Tamias amoenus, Neotamias amoenus (Website 17)
            • Description: Other Rodentia from which POW isolates and/or neutralizing antibodies have been obtained include Columbian ground squirrel, golden mantled ground squirrel, Richardson's ground squirrel, porcupine, chipmunk, meadow mouse, woodland jumping mouse, deer mouse, gray squirrel, eastern chipmunk, and red squirrel (Artsob, 1989).
         6. Yellow-bellied marmot (Website 18):
            • Ontology: UMLS:C1041985
            • GenBank Taxonomy No.: 93162
            • Scientific Name: Marmota flaviventris (Website 18)
            • Description: Neutralization tests revealed POW antibodies in two M. flaviventris (McLean et al., 1971).
         7. Woodchuck (Website 19):
            • Ontology: UMLS:C0043219
            • GenBank Taxonomy No.: 9995
            • Scientific Name: Marmota monax (Website 19)
            • Description: Many small mammals serve as hosts for ixodid ticks. Those implicated in the natural cycle of POW virus include marmots (woodchuck [Marmota monax]) and snowshoe hares, which assist in amplification of both tick and virus populations (Calisher, 1994). Numerous isolates and/or high antibody prevalences have been documented in the woodchuck, Marmota monax (Artsob, 1989).
         8. Meadow vole (Website 20):
            • Ontology: UMLS:C0999657
            • GenBank Taxonomy No.: 10058
            • Scientific Name: Microtus pennsylvanicus (Website 20)
            • Description: 4 out of 59 Microtus pennsylvanicus were found to have antibodies to Powassan virus by hemagglutination-inhibition assay, and 1 out of 49 M. pennsylvanicus tested positive for Powassan virus by a neutralization test (Whitney et al., 1968).
         9. Meadow mouse (Website 49):
            • Ontology: UMLS:C0042947
            • GenBank Taxonomy No.: 10053
            • Scientific Name: Microtus sp (Website 49)
            • Description: Other Rodentia from which POW isolates and/or neutralizing antibodies have been obtained include Columbian ground squirrel, golden mantled ground squirrel, Richardson's ground squirrel, porcupine, chipmunk, meadow mouse, woodland jumping mouse, deer mouse, gray squirrel, eastern chipmunk, and red squirrel (Artsob, 1989).
         10. House mouse (Website 21):
             • Ontology: UMLS:C0025914
             • GenBank Taxonomy No.: 10090
             • Scientific Name: Mus musculus (Website 21)
             • Description: 8 out of 97 Mus musculus were found to have antibodies to Powassan virus by hemagglutination-inhibition assays (Hardy et al., 1974). 15 out of 20 Mus musculus were found to have antibodies to Powassan virus by hemagglutination-inhibition assays (Whitney et al., 1968).
         11. Woodland jumping mouse (Website 22):
             • Ontology: UMLS:C0324957
             • GenBank Taxonomy No.: 101671
             • Scientific Name: Napaeozapus insignis (Website 22)
             • Description: Other Rodentia from which POW isolates and/or neutralizing antibodies have been obtained include Columbian ground squirrel, golden mantled ground squirrel, Richardson's ground squirrel, porcupine, chipmunk, meadow mouse, woodland jumping mouse, deer mouse, gray squirrel, eastern chipmunk, and red squirrel (Artsob, 1989).
         12. Southern grasshopper mouse (Website 23):
             • Ontology: UMLS:C1007687
             • GenBank Taxonomy No.: 38674
             • Scientific Name: Onychomys torridus (Website 23)
             • Description: 1 out of 34 Onychomys torridus was found to have antibodies to Powassan virus by hemagglutination-inhibition assay (Hardy et al., 1974).
         13. Chaetodipus californicus (Website 24):
             • Ontology: UMLS:C1069996
             • GenBank Taxonomy No.: 145408
             • Scientific Name: Chaetodipus californicus (Website 24)
             • Description: 2 out of 8 Chaetodipus (Perognathas) californicus were found to have antibodies to Powassan virus by hemagglutination-inhibition assays (Hardy et al., 1974).
         14. White-footed mouse (Website 25):
             • Ontology: UMLS:C0025937
             • GenBank Taxonomy No.: 10041
             • Scientific Name: Peromyscus leucopus (Website 25)
             • Description: Other isolates of POW virus have been obtained from a red squirrel (Tamiasciurus hudsonicus), a white-footed mouse (Peromyscus leucopus), and a spotted skunk (Spilogale putorius). Their significance in the natural cycle of the virus is unknown; these isolates may reflect only the catholic feeding habits of the tick vectors (Calisher, 1994). Three P. leucopus had monotypic HI titers of 1:40 to Powassan virus (Bast et al., 1973).
         15. Deer mouse (Website 26):
             • Ontology: UMLS:C0025915
             • GenBank Taxonomy No.: 10042
             • Scientific Name: Peromyscus maniculatus (Website 26)
             • Description: Powassan antibody was detected in sera from 107 snowshoe hares (Lepus americanus) or 79 other mammals including 1 deer, 4 flying squirrels (Glaucomys sabrinus), 10 jumping mice (Napaeozapus sp.) 22 deer mice (Peromyscus sp.), 1 mole, 5 shrews, 35 voles or 1 weasel (McLean et al., 1964).
         16. Norway rat (Website 27):
             • Ontology: UMLS:C0034693
             • GenBank Taxonomy No.: 10116
             • Scientific Name: Rattus norvegicus (Website 27)
             • Description: I out of 3 Rattus norvegicus was found to have antibodies to Powassan virus by hemagglutination-inhibition assay (Whitney et al., 1968). Two Norway rats were found to have HI titers of 1:40 to Powassan virus. Another Norway rat had a HI titer of 1:160 to Powassan virus (Bast et al., 1973).
         17. Western harvest mouse (Website 28):
             • Ontology: UMLS:C1011293
             • GenBank Taxonomy No.: 44234
             • Scientific Name: Reithrodontomys megalotis (Website 28)
             • Description: 1 of 14 Reithrodontomys megalotis was found to have antibodies to Powassan virus by hemagglutination-inhibition assay (Hardy et al., 1974).
         18. Gray squirrel (Website 29):
             • Ontology: UMLS:C0324908
             • GenBank Taxonomy No.: 30640
             • Scientific Name: Sciurus carolinensis (Website 29)
             • Description: Other Rodentia from which POW isolates and/or neutralizing antibodies have been obtained include Columbian ground squirrel, golden mantled ground squirrel, Richardson's ground squirrel, porcupine, chipmunk, meadow mouse, woodland jumping mouse, deer mouse, gray squirrel, eastern chipmunk, and red squirrel (Artsob, 1989).
         19. California ground squirrel (Website 31):
             • Ontology: UMLS:C1005339
             • GenBank Taxonomy No.: 34862
             • Scientific Name: Spermophilus beecheyi (Website 31)
             • Description: 16 of 67 Spermophilus (Citellus) beecheyi were found to have antibodies to Powassan virus by hemagglutination-inhibition assays (Hardy et al., 1974).
         20. Columbian ground squirrel (Website 33):
             • Ontology: UMLS:C1015596
             • GenBank Taxonomy No.: 50862
             • Scientific Name: Spermophilus columbianus (Website 33)
             • Description: Other Rodentia from which POW isolates and/or neutralizing antibodies have been obtained include Columbian ground squirrel, golden mantled ground squirrel, Richardson's ground squirrel, porcupine, chipmunk, meadow mouse, woodland jumping mouse, deer mouse, gray squirrel, eastern chipmunk, and red squirrel (Artsob, 1989). 4 out of 60 Citellus columbianus were found to have antibodies to Powassan virus by hemagglutination-inhibition assay (McLean et al., 1970).
         21. Golden-mantled ground squirrel (Website 32):
             • Ontology: UMLS:C1032127
             • GenBank Taxonomy No.: 76772
             • Scientific Name: Spermophilus lateralis (Website 32)
             • Description: Other Rodentia from which POW isolates and/or neutralizing antibodies have been obtained include Columbian ground squirrel, golden mantled ground squirrel, Richardson's ground squirrel, porcupine, chipmunk, meadow mouse, woodland jumping mouse, deer mouse, gray squirrel, eastern chipmunk, and red squirrel (Artsob, 1989).
         22. Richardson's ground squirrel (Website 34):
             • Ontology: UMLS:C1006952
             • GenBank Taxonomy No.: 37591
             • Scientific Name: Spermophilus richardsonii (Website 34)
             • Description: Other Rodentia from which POW isolates and/or neutralizing antibodies have been obtained include Columbian ground squirrel, golden mantled ground squirrel, Richardson ground squirrel, porcupine, chipmunk, meadow mouse, woodland jumping mouse, deer mouse, gray squirrel, eastern chipmunk, and red squirrel (Artsob, 1989).
         23. Eastern chipmunk (Website 30):
             • Ontology: UMLS:C0324910
             • GenBank Taxonomy No.: 45474
             • Scientific Name: Tamias striatus (Website 30)
             • Description: Other Rodentia from which POW isolates and/or neutralizing antibodies have been obtained include Columbian ground squirrel, golden mantled ground squirrel, Richardson ground squirrel, porcupine, chipmunk, meadow mouse, woodland jumping mouse, deer mouse, gray squirrel, eastern chipmunk, and red squirrel (Artsob, 1989).
         24. American red squirrel (Website 35):
             • Ontology: UMLS:C1095776
             • GenBank Taxonomy No.: 10009
             • Scientific Name: Tamiasciurus hudsonicus (Website 35)
             • Description: Other Rodentia from which POW isolates and/or neutralizing antibodies have been obtained include Columbian ground squirrel, golden mantled ground squirrel, Richardson ground squirrel, porcupine, chipmunk, meadow mouse, woodland jumping mouse, deer mouse, gray squirrel, eastern chipmunk, and red squirrel (Artsob, 1989).
         25. Coyote (Website 37):
             • Ontology: UMLS:C0325005
             • GenBank Taxonomy No.: 9614
             • Scientific Name: Canis latrans (Website 37)
             • Description: Serological studies for arboviruses were conducted on 725 animal sera collected in 22 Ontario townships between 1975 and 1980 including 44 coyote (Canis latrans), 277 red fox (Vulpes vulpes), 192 raccoon (Procyon lotor) and 212 striped skunk (Mephitis mephitis). Hemagglutination inhibition antibodies to two flaviviruses, namely St. Louis encephalitis and Powassan were found in 50% of coyote, 47% of skunk, 26% of fox and 10% of raccoon sera (Artsob et al., 1986).
         26. Striped skunk (Website 38):
             • Ontology: UMLS:C0524717
             • GenBank Taxonomy No.: 30548
             • Scientific Name: Mephitis mephitis (Website 38)
             • Description: Serological studies for arboviruses were conducted on 725 animal sera collected in 22 Ontario townships between 1975 and 1980 including 44 coyote (Canis latrans), 277 red fox (Vulpes vulpes), 192 raccoon (Procyon lotor) and 212 striped skunk (Mephitis mephitis). Hemagglutination inhibition antibodies to two flaviviruses, namely St. Louis encephalitis and Powassan were found in 50% of coyote, 47% of skunk, 26% of fox and 10% of raccoon sera (Artsob et al., 1986). In addition, neutralizing antibodies to POW virus have been demonstrated in striped skunk, short- and long-tailed weasel, and raccoon of the order Carnivora and snowshoe hare of the order Lagomorpha (Artsob, 1989).
         27. Ermine (Website 39):
             • Ontology: UMLS:C0325037
             • GenBank Taxonomy No.: 36723
             • Scientific Name: Mustela erminea (Website 39)
             • Description: In addition, neutralizing antibodies to POW virus have been demonstrated in striped skunk, short- and long-tailed weasel, and raccoon of the order Carnivora and snowshoe hare of the order Lagomorpha (Artsob, 1989).
         28. Long-tailed weasel (Website 40):
             • Ontology: UMLS:C0325036
             • GenBank Taxonomy No.: 55048
             • Scientific Name: Mustela frenata (Website 40)
             • Description: In addition, neutralizing antibodies to POW virus have been demonstrated in striped skunk, short- and long-tailed weasel, and raccoon of the order Carnivora and snowshoe hare of the order Lagomorpha (Artsob, 1989).
         29. Raccoon (Website 41):
             • Ontology: UMLS:C0999544
             • GenBank Taxonomy No.: 9654
             • Scientific Name: Procyon lotor (Website 41)
             • Description: Serological studies for arboviruses were conducted on 725 animal sera collected in 22 Ontario townships between 1975 and 1980 including 44 coyote (Canis latrans), 277 red fox (Vulpes vulpes), 192 raccoon (Procyon lotor) and 212 striped skunk (Mephitis mephitis). Hemagglutination inhibition antibodies to two flaviviruses, namely St. Louis encephalitis and Powassan were found in 50% of coyote, 47% of skunk, 26% of fox and 10% of raccoon sera (Artsob et al., 1986). In addition, neutralizing antibodies to POW virus have been demonstrated in striped skunk, short- and long-tailed weasel, and raccoon of the order Carnivora and snowshoe hare of the order Lagomorpha (Artsob, 1989).
         30. Eastern spotted skunk (Website 42):
             • Ontology: UMLS:C1003284
             • GenBank Taxonomy No.: 30552
             • Scientific Name: Spilogale putorius (Website 42)
             • Description: Other isolates of POW virus have been obtained from a red squirrel (Tamiasciurus hudsonicus), a white-footed mouse (Peromyscus leucopus), and a spotted skunk (Spilogale putorius). Their significance in the natural cycle of the virus is unknown; these isolates may reflect only the catholic feeding habits of the tick vectors (Calisher, 1994).
         31. Gray fox (Website 43):
             • Ontology: UMLS:C0993590
             • GenBank Taxonomy No.: 55040
             • Scientific Name: Urocyon cinereoargenteus (Website 43)
             • Description: Urocyon cinereoargenteus has been found to be infected with Powassan virus in New York (Artsob, 1989). An additional strain of POW virus was isolated from the brain of a gray fox. The brain was received by the Rabies Group of the Laboratories for Veterinary Science of this Division on July 1. The animal had been found with choreiform movements in Broome County 48 hours before it had died. The brain suspension was inoculated intracerebrally into 10- to 12-g mice July 1, and an infectious agent was isolated which was submitted in its 4th passage to use for identification. In suckling mice the titer was 10(8.5) LD(50) per 0.03 ml smb suspension. Two immune rabbit sera, one prepared with POW and the other with strain 64-7062, protected all of 16 mice inoculated with 40 LD(50) of the fox strain (Whitney and Jamnback, 1965).
         32. Red fox (Website 44):
             • Ontology: UMLS:C0325013
             • GenBank Taxonomy No.: 9627
             • Scientific Name: Vulpes vulpes (Website 44)
             • Description: Serological studies for arboviruses were conducted on 725 animal sera collected in 22 Ontario townships between 1975 and 1980 including 44 coyote (Canis latrans), 277 red fox (Vulpes vulpes), 192 raccoon (Procyon lotor) and 212 striped skunk (Mephitis mephitis). Hemagglutination inhibition antibodies to two flaviviruses, namely St. Louis encephalitis and Powassan were found in 50% of coyote, 47% of skunk, 26% of fox and 10% of raccoon sera (Artsob et al., 1986).
         33. Snowshoe hare (Website 45):
             • Ontology: UMLS:C1013735
             • GenBank Taxonomy No.: 48086
             • Scientific Name: Lepus americanus (Website 45)
             • Description: Many small mammals serve as hosts for ixodid ticks. Those implicated in the natural cycle of POW virus include marmots (woodchuck [Marmota monax]) and snowshoe hares, which assist in amplification of both tick and virus populations (Calisher, 1994). In addition, neutralizing antibodies to POW virus have been demonstrated in striped skunk, short- and long-tailed weasel, and raccoon of the order Carnivora and snowshoe hare of the order Lagomorpha (Artsob, 1989).
         34. Black-tailed jackrabbit (Website 46):
             • Ontology: UMLS:C1013736
             • GenBank Taxonomy No.: 48087
             • Scientific Name: Lepus californicus (Website 46)
             • Description: 4 out of 100 Lepus californicus were found to have antibodies to Powassan virus by hemagglutination-inhibition assays (Hardy et al., 1974).
         35. Desert cottontail (Website 47):
             • Ontology: UMLS:C1003290
             • GenBank Taxonomy No.: 30581
             • Scientific Name: Sylvilagus auduboni (Website 47)
             • Description: 3 of 50 Sylvilagus auduboni were found to have antibodies to Powassan virus by hemagglutination-inhibition assays (Hardy et al., 1974).
         36. Southern opossum (Website 48):
             • Ontology: UMLS:C0999405
             • GenBank Taxonomy No.: 9268
             • Scientific Name: Didelphis marsupialis (Website 48)
             • Description: One Didelphis marsupialis was found to have antibodies to Powassan virus by hemagglutination-inhibition assay (Hardy et al., 1974).
         37. Dog (Website 51):
             • Ontology: UMLS:C0012984
             • GenBank Taxonomy No.: 9615
             • Scientific Name: Canis familiaris (Website 51)
             • Description: Serologic surveys and virus isolations have shown infections in wild mammals, including rodents, hares, dogs, skunks, and foxes (Burke and Monath, 2001). Other research provided evidence of latent infection with POWV in humans, domestic pets (cats, dogs, goats) and local rodents (Gritsun et al., 2003b).
         38. Birds (Website 56):
             • Ontology: UMLS:C0005595
             • GenBank Taxonomy No.: 8782
             • Scientific Name: Aves (Website 56)
             • Description: Isolations of POW virus have been reported in several species of birds in the U.S.S.R. including mallard, common teal, pintail, and masked bunting. Kilenko et al. tested sera from 190 U.S.S.R. birds by HI and found antibodies in four birds, all of different species. No significant evidence exists for POW virus infection of North American birds (Artsob, 1989).
         39. Natrix (Website 58):
             • Ontology: UMLS:C0206280, C0327374
             • GenBank Taxonomy No.: 8583
             • Scientific Name: Natrix (Website 58)
             • Description: Eight snakes were collected throughout the year. the following three species were represented: 6 Thamnops sirtalis (garter snake), I Thamnopsis sauriti sauritus (ribbon snake), and 1 Natrix sipedo (red bellied water snake). The water snake had a HI titer of 1:20 to Powassan virus. There were no virus isolations from either the liver or brain of any of the snakes listed above (Bast et al., 1973).
         40. Red-bellied snake (Website 59):
             • Ontology: UMLS:C1012511
             • GenBank Taxonomy No.: 46282
             • Scientific Name: Storeria occipitomaculata (Website 59)
             • Description: A single Storeria occipitomaculata was found to have antibodies to Powassan virus by hemagglutination-inhibition assay (Whitney et al., 1968).
         41. Eastern garter snake (Website 60):
             • Ontology: UMLS:C1005396
             • GenBank Taxonomy No.: 35019
             • Scientific Name: Thamnophis sirtalis (Website 60)
             • Description: 3 out of 6 Thamnophis sirtalis were found to have antibodies to Powassan virus by hemagglutination-inhibition assay. 1 out of 6 Thamnophis sirtalis was found to have antibodies to Powassan virus by neutralization test (Whitney et al., 1968).
         42. Eastern painted turtle (Website 61):
             • Ontology: UMLS:C0999071
             • GenBank Taxonomy No.: 8479
             • Scientific Name: Chrysemys picta (Website 61)
             • Description: 2 out of 43 Chrysemys picta were found to have antibodies to Powassan virus by hemagglutination-inhibition assay. 1 out of 43 Chrysemys picta was found to have antibodies to Powassan virus by neutralization test (Whitney et al., 1968).
         43. American toad (Website 62):
             • Ontology: UMLS:C0327034
             • GenBank Taxonomy No.: 8389
             • Scientific Name: Bufo americanus (Website 62)
             • Description: Three Bufo americanus were found to have antibodies to Powassan virus by hemagglutination-inhibition assay (Whitney et al., 1968).
         44. Green frog (Website 63):
             • Ontology: UMLS:C1069947
             • GenBank Taxonomy No.: 145282
             • Scientific Name: Rana clamitans (Website 63)
             • Description: 4 out of 13 Rana clamitans were found to have antibodies to Powassan virus by hemagglutination-inhibition assay (Whitney et al., 1968). Eight amphibians were captured, with two species represented: four Rana catesbeiana (bull frog) and four Rana clamitans (green frog). One green frog had a HI titer of 1:20 to Powassan virus. Tissues from these amphibians were negative in isolation attempts (Bast et al., 1973).
         45. Pickerel frog (Website 64):
             • GenBank Taxonomy No.: 298395
             • Scientific Name: Rana palustris (Website 64)
             • Description: 3 out of 4 Rana palustris were found to have antibodies to Powassan virus by hemagglutination-inhibition assay (Whitney et al., 1968).
         46. Northern leopard frog (Website 65):
             • Ontology: UMLS:C0034653
             • GenBank Taxonomy No.: 8404
             • Scientific Name: Rana pipiens (Website 65)
             • Description: 7 out of 15 >Rana pipiens were found to have antibodies to Powassan virus by hemagglutination-inhibition assay (Whitney et al., 1968).
      
      
   2. Infection Process:
      
      No infection process information is currently available here.
      
      
   3. Disease Information:
      
      No disease information is currently available here.
      
      
   4. Prevention:
      
      No prevention information is currently available here.
      
      
   5. Model System:
      
      No model system information is currently available here.
      
      

IV. Labwork Information

A. Biosafety Information:

1. Biosafety information for : Powassan virus :
   • Biosafety Level: 3 (Website 52)
   • Applicable:
   • Precautions:
     • Biosafety Level 3 practices, safety equipment, and facilities are recommended for activities using potentially infectious clinical materials and infected tissue cultures, animals, or arthropods (Website 53).

B. Culturing Information:

1. Cytopathic effects :
   1. Description: POW virus produced cytopathic effects and/or plaques in several vertebrate cell lines including baby hamster kidney, BHK-21, rhesus monkey kidney, LLC-MK2, African green monkey kidney, VERO primary swine kidney, and human embryo lung, WI-38 (Mayflick) cells. Growth of POW virus without cytopathic effect occurred in primary chick embryo, rhesus monkey kidney, and primary cells from the ticks, Hyalomma dromedarii and D. silvarum. POW virus did not propagate in mosquito, Culex tarsalis and Ae. aegypti nor in the emperor gum worm, Antherae eucalypti cell culture. Isolation procedures for POW virus have employed i.c. inoculation of suckling mice almost exclusively; however, McLean et al. used primary swine kidney cells to reisolate and titrate POW virus in tick pools and clotted blood from which virus had originally been isolated using suckling mice (Artsob, 1989). Other tissue cultures used to test for POW N antibodies have included BHK-21 and WI-38 (Artsob, 1989).
      
      

C. Diagnostic Tests :

1. Organism Detection Tests:
   
   No organism detection tests available here.
   
   
2. Immunoassay Tests:
   1. Hemagglutination inhibition assay:
      1. Ontology: UMLS:C0018905
      2. Time to Perform: unknown
      3. Description: Currently in Ontario the Provincial Health Laboratory performs a hemagglutination inhibition assay on acute and convalescent sera for Powassan virus antibody. Although the test will cross-react with antibodies of other flaviviruses such as dengue, St. Louis encephalitis and yellow fever, an epidemiologic history of the patient should help distinguish among them. The major drawback is that the detection of seroconversion may require a week or more, delaying diagnosis (Ralph, 1999). Hemagglutination-inhibition tests were performed in plastic plates. Unheated serums were absorbed with kaolin to remove inhibitors of hemagglutination, and naturally occurring agglutinins were removed by absorption with chick cells. Antigens were prepared by extraction of infected suckling mouse brains with borate saline, pH 9.3, centrifugation at 10,000 rpm for 1 hour, and treatment of the resultant supernatant with 2.5 mg per ml protamine. Serum-virus mixtures diluted in borate saline, pH 9, containing 0.4% bovine serum albumin were held at 4 C overnight before addition of a 0.25% suspension of erythrocytes from newly hatched chicks. Erythrocytes were diluted in virus-adjusting diluent to give a final pH of 6.4 for eastern equine encephalomyelitis antigen and 6.7 for Powassan antigen (McLean et al., 1961).
   2. EIA-IC:
      1. Ontology: UMLS:C0086231
      2. Description: Comparative titrations of alpha-, flavi- and Bunyamwera viruses were made by EIA-IC and according to cytopathic effect (CPE). Specific enzymatic reactions appeared earlier and in higher titres than CPE. The titres of dengue type 1, Mayaro, Powassan and Langat viruses measured by EIA-IC were comparable to those measured by intracerebral inoculation of mice. The cross-reactivity testing of EIA-IC among alphaviruses (Chikungunya, Sindbis and Mayaro), flaviviruses (Japanese encephalitis, Murray valley encephalitis, Kunjin, West Nile, yellow fever and louping ill, Powassan, Langat) and Bunyamwera arboviruses using polyclonal immune ascitic fluids confirmed the high specificity of EIA-IC. Homologous reactions mostly showed higher titres than heterologous ones. No cross-reactivity was seen between alpha-, flavi- and bunyaviruses, among the three alphaviruses, between mosquito-borne and tick-borne flaviviruses, or between JE complex and YF viruses. However, a cross-reactivity to different extent was observed among the four JE complex viruses and among louping ill, Powassan and Langat viruses. The results of EIA-IC cross tests showed that this method can distinguish togavirus group- or species-specific antigens, more precisely than conventional ELISA (Xiao et al., 1986).
   3. Neutralization tests for PV:
      1. Ontology: UMLS:C0201677
      2. Time to Perform: unknown
      3. Description: Neutralization tests were performed by intracerebral inoculation of serum-virus mixtures into 3-week-old mice. Mixtures containing 0.1 ml aliquots of unheated test serum, unheated normal ox serum ("accessory factor"), and Powassan virus diluted in 10% ox serum saline to give a final concentration of 50 to 100 mouse LD(50) were held at room temperature (22 C) for 1 hour. Groups of 5 mice were inoculated intracerebrally with 0.03 ml aliquots of each serum-virus mixture. Serums which neutralized at least 50 LD(50) of virus were considered positive (McLean et al., 1961).
   4. Complement Fixation test:
      1. Ontology: UMLS:C0009541
      2. Time to Perform: unknown
      3. Description: Whenever sufficient serum was available, complement-fixation tests were performed against the antigens of six arboviruses: Powassan, Silverwater, California, Colorado tick fever, Tensaw and eastern equine encephalomyelitis (EEE), prepared by extraction of infected suckling mouse brains with borate-saline solution of pH 9.3 (McLean et al., 1964).
   
   
3. Nucleic Acid Detection Tests: :
   1. PCR for Flavivirus Amplification (Meiyu et al., 1997):
      1. Time to Perform: 1-to-2-days
      2. Description: Using a universal primer set designed to match the sequence of the NS1 gene of flaviviruses, the virus RNA of dengue (DEN), Japanese encephalitis (JEV), powassan and langat of Flaviviridae were successfully amplified by polymerase chain reaction (PCR) via cDNA; and with different internal primers, the serotypes of the dengue viruses were identified. Of the 78 clinically diagnosed dengue fever patients, 18 patients were positive for DEN 1, 48 patients for DEN 2 and 8 patients concurrently infected with DEN 4. Of the 52 patients admitted with Japanese encephalitis (JE), 45 were determined to be JEV infections. By nested PCR, we completed the identification of flaviviruses within 2 days. The results show that seven primers have a potential value for rapid clinical diagnosis of flavivirus infections (Meiyu et al., 1997).
      3. Primers:
         • DJS(+) and DJA(-)
           • Forward: DJS(+) GACATGGGGTATTGGAT (Meiyu et al., 1997)
           • Reverse: DJA(-) TCCATCCCATACCTGCA (Meiyu et al., 1997)
           • Product
             • Size: 413
   2. RT-PCR:
      1. Ontology: UMLS:C0599161
      2. Time to Perform: unknown
      3. Description: Viral RNA was detected using a quantitative real-time reverse transcriptase-polymerase reaction (RT-PCR) using primers (forward: 5' - gtgactggctatttgagcacctt-3', reverse: 5'-tggatctaaccttcgctatgaattc-3') designed to amplify an 83-base pair region of the POW virus nonstructural protein 5 coding region, and a probe (5'-6FAM-cgagccagggtga-MGBNFQ-3') designed to specifically bind all known linage II POW virus strains (Ebel et al., 2004).
      4. Primers:
         • • Forward: Forward: 5' - gtgactggctatttgagcacctt-3 (Ebel et al., 2004)
           • Reverse: Reverse: 5'- tggatctaaccttcgctatgaattc-3' (Ebel et al., 2004)
           • Real-time-probe: 5'-6FAM-cgagccagggtga-MGBNFQ-3' (Ebel et al., 2004)
           • Product
             • Name:
             • Size: 83 bp
             • Product GenBank Accession Number:
   
   
4. Other Types of Diagnostic Tests:
   
   No other tests available here.
   
   

V. References

A. Journal References:

Artsob et al., 1986: Artsob H, Spence L, Th'ng C, Lampotang V, Johnston D, MacInnes C, Matejka F, Voigt D, Watt I. Arbovirus infections in several Ontario mammals, 1975-1980. Can J Vet Res. 1986; 50(1): 42 - 46. [PubMed: 3017527].

Bast et al., 1973: Bast TF, Whitney E, Benach JL Considerations on the ecology of several arboviruses in eastern Long Island. Am J Trop Med Hyg. 1973; 22(1): 109 - 115. [PubMed: 4684881].

Calisher, 1994: Calisher CH Medically important arboviruses of the United States and Canada. Clin Microbiol Rev. 1994; 7(1): 89 - 116. [PubMed: 8118792].

Chambers et al., 1990: Chambers TJ, Hahn CS, Galler R, Rice CM. Flavivirus genome organization, expression, and replication. Annu Rev Microbiol. 1990; 44(): 649 - 688. [PubMed: 2174669].

Costero and Grayson, 1996: Costero A, Grayson MA Experimental transmission of Powassan virus (Flaviviridae) by Ixodes scapularis ticks (Acari:Ixodidae). Am J Trop Med Hyg. 1996; 55(5): 536 - 546. [PubMed: 8940987].

Ebel et al., 2004: Ebel GD, Kramer LD Short report: duration of tick attachment required for transmission of powassan virus by deer ticks. Am J Trop Med Hyg. 2004; 71(3): 268 - 271. [PubMed: 15381804].

Frolova et al., 1985: Frolova MP, Isachkova LM, Shestopalova NM, Pogodina VV. Experimental encephalitis in monkeys caused by the Powassan virus. Neurosci Behav Physiol. 1985; 15(1): 62 - 69. [PubMed: 2987750].

Gholam et al., 1999: Gholam BIA, Puksa S, Provias JP Powassan encephalitis: a case report with neuropathology and literature review. CMAJ. 1999; 161(11): 1419 - 1422. [PubMed: 10906899].

Gritsun et al., 2003: Gritsun TS, Nuttall PA, Gould EA Tick-borne flaviviruses. Adv Virus Res. 2003; 61: 317 - 371. [PubMed: 14714436].

Gritsun et al., 2003b: Gritsun TS, Lashkevich VA, Gould EA Tick-borne encephalitis. Antiviral Res. 2003; 57(1-2): 129 - 146. [PubMed: 12615309].

Hardy et al., 1974: Hardy JL, Reeves WC, Scrivani RP, Roberts DR. Wild mammals as hosts of group A and group B arboviruses in Kern County, California. A five-year serologic and virologic survey. Am J Trop Med Hyg. 1974; 23(6): 1165 - 1177. [PubMed: 4429186].

Khozinskaia and Pogodina, 1982: Khozinskaia GA, Pogodina VV Modeling of mixed infection by tick-borne encephalitis and Powassan viruses in mice. Vopr Virusol. 1982; 27(4): :491 - :495. [PubMed: 6291250].

Kuno et al., 2001: Kuno G, Artsob H, Karabatsos N, Tsuchiya KR, Chang GJ. Genomic sequencing of deer tick virus and phylogeny of powassan-related viruses of North America. Am J Trop Med Hyg. 2001; 65(5): 671 - 676. [PubMed: 11716135].

Lessell and Collins, 2003: Lessell S, Collins TE Ophthalmoplegia in Powassan encephalitis. Neurology. 2003; 60(10): 1726 - 1727. [PubMed: 12771287].

Little et al., 1985: Little PB, Thorsen J, Moore W, Weninger N. Powassan viral encephalitis: a review and experimental studies in the horse and rabbit. Vet Pathol. 1985; 22(5): 500 - 507. [PubMed: 2996203].

Mandl et al., 1993: Mandl CW, Holzmann H, Kunz C, Heinz FX. Complete genomic sequence of Powassan virus: evaluation of genetic elements in tick-borne versus mosquito-borne flaviviruses. Virology. 1993; 194(11): 173 - 184. [PubMed: 8097605].

McLean et al., 1961: McLean DM, Walker SJ, MacPherson LW, Scholten TH, Ronald K, Wyllie JC, McQueen EJ. Powassan virus: investigations of possible natural cycles of infection. J Infect Dis. 1961; 109(): 19 - 23. [PubMed: 13774094].

McLean et al., 1964: McLean DM, de Vos A, Quantz EJ Powassan virus: Field investigations during the summer of 1963. Am J Trop Med Hyg. 1964; 13(4-6): 747 - 753. [PubMed: 14205898].

McLean et al., 1970: McLean DM, Crawford MA, Ladyman SR, Peers RR, Purvin-Good KW.. California encephalitis and Powassan virus activity in British Columbia, 1969. Am J Epidemiol.. 1970; 92(4): 266 - 272. [PubMed: 5466318].

McLean et al., 1971: McLean DM, Bergman SK, Gooddard EJ, Graham EA, Purvin-Good KW. North-south distribution of arbovirus reservoirs in British Columbia, 1970. Can J Public Health. 1971; 62(2): 120 - 124. [PubMed: 5572708].

Meiyu et al., 1997: Meiyu F, Huosheng C, Cuihua C, Xiaodong T, Lianhua J, Yifei P, Weijun C, Huiyu G. Detection of flaviviruses by reverse transcriptase-polymerase chain reaction with the universal primer set.. Microbiol Immunol. 1997; 41(3): 209 - 213. [PubMed: 9130232].

MMWR, 2001: Outbreak of Powassan encephalitis--Maine and Vermont, 1999-2001. MMWR Morb Mortal Wkly Rep. 2001; 50(35): 761 - 764. [PubMed: 11787585].

Ralph, 1999: Ralph ED Powassan encephalitis. CMAJ. 1999; 161(11): 1416 - 1417. [PubMed: 10906898].

Whitney and Jamnback, 1965: Whitney E, Jamnback H The first isolations of Powassan virus in New York state. Proc Soc Exp Biol Med. 1965; 119(): 432 - 435. [PubMed: 14328910].

Whitney et al., 1968: Whitney E, Jamnback H, Means RG, Watthews TH. Arthropod-borne-virus survey in St. Lawrence County, New York. Arbovirus reactivity in serum from amphibians, reptiles, birds, and mammals. Am J Trop Med Hyg. 1968; 17(4): 645 - 650. [PubMed: 5691616].

Woodall and Roz, 1977: Woodall JP, Roz A Experimental milk-borne transmission of Powassan virus in the goat. Am J Trop Med Hyg.. 1977; 21(6): 190 - 192. [PubMed: 190910].

Xiao et al., 1986: Xiao ZS, Jia LL, Qu XS, Zhang YH. Application of enzyme immunoassay on infected cells (EIA-IC) for arboviruses. Acta Virol.. 1986; 30(6): 487 - 493. [PubMed: 2881468].

B. Book References:

Artsob, 1981: Artsob H Powassan Encephalitis. 156 - 158. In: Steele JH. CRC Handbook Series in Zoonoses. Section B: Viral ZoonosesVolume I.1981. CRC Press, Inc., Boca Raton, Florida.

Artsob, 1989: Artsob H Powassan encephalitis. 29 - 49. In: Monath TP The Arboviruses: Epidemiology and Ecology. Volume IV.1989. CRC Press, Boca Raton, Florida.

Burke and Monath, 2001: Burke DS, Monath TP Flaviviurses. 1043 - 1125. In: Knipe DM, Howley PM Fields Virology.2001. Lippincott Williams and Wilkins, Philadelphia Pa.

C. Website References:

Website 1: Powassan virus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=11083&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 2: Tick-borne powassan virus (strain lb) [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=39008&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 3: Powassan virus, complete genome. [ http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?db=nucleotide&val=20260779 ].

Website 4: Powassan virus, complete genome [ http://www.ncbi.nlm.nih.gov/genomes/framik.cgi?db=genome&gi=16176 ].

Website 5: Dermacentor andersoni [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=34620&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 6: Dermacentor variabilis [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=34621&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 7: Ixodes angustus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=35564&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 8: Ixodes persulcatus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=34615&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 9: Ixodes cookei [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=35565&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 10: Ixodes scapularis [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=6945&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 11: Ixodes spinipalpis [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=34614&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 12: Ochlerotatus togoi [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=55967&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 13: Anopheles hyrcanus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=138534&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 14: Haemaphysalis [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=34622&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 15: Dipodomys heermanni [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=10018&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 16: Erethizon dorsatum [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=34844&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 17: Tamias amoenus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=64679&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 18: Marmota flaviventris [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=93162&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 19: Marmota monax [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=9995&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 20: Microtus pennsylvanicus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=10058&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 21: Mus musculus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=10090&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 22: Napaeozapus insignis [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=101671&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 23: Onychomys torridus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=38674&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 24: Chaetodipus californicus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=145408&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 25: Peromyscus leucopus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=10041&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 26: Peromyscus maniculatus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=10042&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 27: Rattus norvegicus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=10116&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 28: Reithrodontomys megalotis [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=44234&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 29: Sciurus carolinensis [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=30640&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 30: Tamias striatus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=45474&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 31: Spermophilus beecheyi [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=34862&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 32: Spermophilus lateralis [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=76772&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 33: Spermophilus columbianus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=50862&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 34: Spermophilus richardsonii [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=37591&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 35: Tamiasciurus hudsonicus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=10009&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 36: Zapus hudsonius [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=160400&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 37: Canis latrans [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=9614&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 38: Mephitis mephitis [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=30548&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 39: Mustela erminea [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=36723&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 40: Mustela frenata [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=55048&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 41: Procyon lotor [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=9654&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 42: Spilogale putorius [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=30552&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 43: Urocyon cinereoargenteus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=55040&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 44: Vulpes vulpes [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=9627&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 45: Lepus americanus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=48086&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 46: Lepus californicus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=48087&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 47: Sylvilagus audubonii [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=30581&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 48: Didelphis marsupialis [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=9268&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 49: Microtus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=10053&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 50: Homo sapiens [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=9606&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 51: Canis familiaris [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=9615&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 52: BMBL Section VII. Agent Summary Statements. Section VII: Table 4 - Arboviruses and Certain Other Viruses Assigned to Biosafety Level 3 [ http://www.cdc.gov/od/ohs/biosfty/bmbl4/bmbl4s74.htm ].

Website 53: BMBL Section VII. Arboviruses and Arenaviruses Assigned to Biosafety Level 3 [ http://www.cdc.gov/od/ohs/biosfty/bmbl4/bmbl4s7h.htm ].

Website 54: Ammospermophilus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=45485&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 55: Dipodomys [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=10016&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 56: Aves [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=8782&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 57: Rana clamitans [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=8782&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 58: Natrix [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=8583&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 59: Storeria occipitomaculata [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&:id=46282&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 60: Thamnophis sirtalis [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=35019&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 61: Chrysemys picta [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=8479&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 62: Bufo americanus [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=8389&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 63: Rana clamitans [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=145282&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 64: Rana palustris [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=298395&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 65: Rana pipiens [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=8404&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

Website 66: Rana clamitans [ http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=145282&lvl=3&lin=f&keep=1&srchmode=1&unlock ].

D. Thesis References:

No thesis or dissertation references used.

VI. Curation Information

• Curators: Rebecca Wattam (wattam@vbi.vt.edu)
• Date: 09/26/04
• Version: 0.83
• Note:
• Contact information:
  • Email: pathinfo@vbi.vt.edu
  • Telephone:
  • Address: