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| POWASSAN VIRUS & DEER TICK VIRUS |
| POW virus and DTV are members of the viral family Flaviviridae, genus flavivirus, and are memebers of the tick-borne encephalitis (TBE) complex. POW virus was first isolated in 1958 in Powassan, Ontario - from the brain of a 5 year old boy who had developed encephalitis and died. DTV was first discovered in 1996 in Massachusetts and Connecticut, no known human disease is currently associated with DTV. DTV and POW virus are closely related and it is believed that DTV may be a subtype of POW virus. DTV is vectored primarily by the deer ticks Ixodes dammini and I. scapularis; POW by I. cookei - which feeds mostly on groundhogs. |
| INFECTIONS |
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| POW: > First case in U.S. in 1970 (New Jersey) >1958-1998: 27 cases human POW reported from Canada and northeaster U.S. >1999-2001: 4 new cases in Maine and Vermont >One of least common causes of arbovirus encephalitis, but has the highest case-fatality rate |
| DTV: >First discovered in 1996 >Consequences of infection are unknown >May derive from POW virus >Most members of TBE complex tend to be virulent w/ encephalitis fatality rates of 40%. This leads to concern over possible human exposure to DTV. |
| INFECTION: >May occur between May and December >Greatest risk in June-September when ticks are most active >Males and children (under age 15) most frequently bitten >Incubation for POW is 8-34 days >Initial symptoms include sore throat, sleepiness, headache, disorientation >Encephalitis characterized by vomiting, respiratory distress, convulsions, sustained fever. >During acute phase, lethargy common, semi-comatose state, and paralysis |
| GENOMICS & PHYLOGENY |
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| Flaviviruses: >Have a genome ~11 kb in size >Single open reading frame (ORF) > ORF is translated to one polyprotein and is cleaved by viral encoded proteases and cellular proteases. >Enveloped >Structural proteins include nucleocapsid and envelope glycoproteins >All flaviviruses share significant amino acid homology - resulting in serological cross reactivity |
| Comparison of POW virus & DTV >DTV genome is 10,800 bases - one base shorter than POW virus >Nucleotide sequence identity between POW & DTV is approximately 84% >Coding sequence of DTV and POW encodes for 3,416 amino acids >Amino acid difference between the two viruses is 6% >POW and DTV may share the same origin |
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| Phylogeny: >Phylogenetic construction of POW virus done using env gene, ns-5 gene, and 3' untranslated region of DTV & POW >Study yielded 2 lineages of POW virus >Lineage 1 was isolates from I. cookei, groundhogs, human brain & squirrels; all samples from New York and Canada. >Lineage 2 was isolates from deer ticks, one fox, white-footed mice; all samples from Atlantic coast of U.S. and state of Wisconsin. >2 lineages assumed to be result of changes in the envelope gene. Changes are related to different modes of perpetuations. >Lineage 1 seems to be classic POW >Lineage 2 is the subtype DTV |
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| IMMUNODIAGNOSTIC DEVELOPMENT |
| Current Situation: >No vaccines or anti-viral therapies available for POW encephalitis >Lab tests not commercially available >Specimens must be sent to state health departments or National Centers for Disease Control for testing >Researchers have traditionally used neutraliztion tests. These are not always easy to use. Members of the TBE complex are Level 3-4 viruses and require high levels of biocontainment. Not all facilities and labs have this. >Other methods for testing are hemagglutination-inhibition assay, complement fixation, immunofluoresence, ELISA. Problems of cross-reactivity arise with these tests. |
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| Developing Other Tests: >One study cloned a portion of the DTV envelope gene and expressed it in E. coli >It was then used in ELISA and Westerns >Viral RNA was isolated from suckling mouse brains infected with DTV and then reverse transcribed >Primers were used to obtain the portion of the DTV envelope gene in frame with XhoI and Hind III restriction sites >Reaction products were electrophoresed, purified, and ligated into a pCR plasmid >Plasmid was cut with XhoI & Hind III, separated, purified and put into pET23b and transformation was done >The recombinant DTV envelope gene was used in ELISA and Westerns to test for detection of Ab's to DTV & POW >Although successful, the test cannot not distinguish between DTV and POW - it only proves the virus(es) is present |
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| WHY STUDY POW & DTV? |
| Reasons: |
| >To help prevent risk of transmission >To make public aware as population expands into areas for industrial & recreational use - areas that may harbor large numbers of ticks >To prevent transmission to domestic animals - dogs, cats, cows, horses, etc. >To enhance development of vaccines, anti-viral therapy, and diagnostic tests |
| SUPER LINKS |
| REFERENCES |
| 1. Ebel GD, Foppa I, Spielman A, Telford SR. A Focus of Deer Tick Virus Transmission in the Northcentral United States. Emerging Infectious Disease. 1999; July-August: 5(4): 570-573. 2. Ebel GD, Campbell EN, Goethert HK, Spielman A, Telford SR. Enzootic Transmission of Deer Tick Virus In New England And Wisconsin Sites. Am J Trop Med Hyg. 2000; 63(1,2): 36-42. 3. Ebel GD, Spielman A, Telford SR. Phylogeny of North American Powassan Virus. J Gen Vir. 2001; 82: 1657-1665. 4. EID Dispatch. A New Tick-borne Encephalitis-like Virus Infecting New England Deer Ticks, Ixodes dammini. Emerging Infectious Disease. 1997; April-June: 3(2): 165-170. 5. Gholam BIA, Puksa S, Provias JP. Powassan Encephalitis: a case report with neuropathology and literature review. Can Med Ass J. 1999; 161(11): 1419-1422. 6. Kuno G, Artsob H, Karabatsos N, Tsuchiya KR, Chang GJJ. 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. 7. Morbidity and Mortality Weekly Report. Outbreak of Powassan Encephalitis---Maine and Vermont, 1999--2001. September 07, 2001; 50(35): 761-764. 8. Ralph ED. Powassan encephalitis. JAMC. 1999; 161(11): 1416-1417. 9. Strauss JH, Strauss EG. Viruses and Human Disease. Academic Press, San Diego, CA 2002. Chapter 3: 57-122. 10. United States Army Center for Health Promotion and Preventive Medicine (USACHPPM). chppm-www.apgea.army.mil. Just the Facts.....Powassan Encephalitis. May 2002. |
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