My research interests lie in elucidating the molecular mechanisms by which herpesviruses cause infections and disease. Herpes viruses establish latent infections in long-lived differentiated cells and reactivate in response to a variety of stressors. The long-term objective of our laboratory is to determine how herpes simplex viruses (HSV), which become latent in sensory neurons, recognize when their hosts are stressed.
A few years ago our laboratory identified two neuronal proteins that have the ability to influence viral gene expression. Both Luman and Zhangfei are basic leucine-zipper proteins. Luman can activate vital genes needed for the initiation of the HSV replicative cycle. Zhangfei suppresses both the activity of Luman and HSV gene expression. We are testing the hypothesis that Luman and Zhangfei regulate the neuron's response to stress and that HSV have evolved to use the proteins to influence viral latency and reactivation.
We are also examining the role bats play in emerging viral diseases. Our group has identified unique polyoma and coronaviruses in Canadian bats, and we are studying the potential role of these and other pathogens in diseases of human and domestic animals.
Misra V, Dumonceaux T, Dubois J, Willis C, Nadin-Davis S, Severini A, Wandeler A, Lindsay R, Artsob H. 2009. "Detection of polyoma and corona viruses in bats of Canada." Journal of General Virology. 90: 2015-2022. Epub 2009 Apr 8.
Valderrama X, Rapin N, Verge VM, Misra V. 2009. "Zhangfei induces the expression of the nerve growth factor receptor, trkA, in medulloblastoma cells and causes their differentiation or apoptosis." Journal of Neurooncology. 91(1): 7-17. Epub 2008 Aug 22.
Valderrama X, Rapin N, Misra V. 2008. "Zhangfei, a novel regulator of the human nerve growth factor receptor, trkA." Journal of Neurovirology. 14(5): 425-36. Epub 2008 Nov 18.
Akhova O, Bainbridge M, and Misra V. 2005. The neuronal host cell factor-binding protein Zhangfei inhibits herpes simplex virus replication. Journal of Virology. 79: 14708-14718
Misra V, Rapin N, Akhova O, Bainbridge M, Korchinski P. 2005. “Zhangfei is a potent and specific inhibitor of the HCF-binding transcription factor Luman.” Journal of Biological Chemistry. Published on-line before print.
Moshynska O, Moshynskyy I, Misra V, Saxena A. 2005. “G125A single-nucleotide polymorhism in the human BAX promoter affects gene expression.” Oncogene. Published on-line.
Raggo C, Rapin N, Sterling J, Gobeil P, Smith-Windsor E, O'Hare P, Misra V. 2002. “Luman, the cellular homologue of HSV VP16 is processed by regulated intra-membrane proteolysis (RIP).” Molecular and Cellular Biology. 22: 5639-5649.
Syed NA, Horner KN, Misra V, Khandelwal RL. 2002. “Different cellular localization, translocation and insulin-induced phosphorylation of PKBa in HepG2 cells and hepatocytes.” The Journal of Cellular Biochemistry. 86: 118-127.
Christensen CR, Kowalski J, Chedrese PJ, Misra V, Laarveld B, Redmond MJ. 2002. “Characterization of a recombinant porcine follistatin in a heat shock expression system.” Canadian Journal of Animal Science. (in press).
Lu R, Misra V. 2000. “Potential role for Luman, the cellular homologue of herpes simplex virus VP16 (a gene trans-inducing factor), in herpesvirus latency.” Journal of Virology. 74: 934-943.
Lu R, Misra V. 2000. “Zhangfei, a second HCF-binding protein interacts with herpes simplex virus accessory factor HCF in a manner similar to HCF.” Nucleic Acids Research. 28: 2446-2454.
Lu R, Yang P, Padmakumar S, Misra V. 1998. “The herpesvirus transactivator VP16 mimics a human basic domain leucine-zipper protein, Luman, in its interactions with HCF." Journal of Virology. 72: 6291-6297.
Lu R, Yang P, O'Hare P, Misra V. 1997. “Luman, a new member of CREB/ATF family, binds to the herpes simplex virus VP16 associated host cellular factor (HCF).” Molecular and Cellular Biology. 17: 5117-5126.
Schwyzer M, Styger D, Vogt B, Lowery DE, Simard C, LaBoissiere S, Misra V, Vlcek C, Paces V. 1996. “Gene contents in a 31 kb segment at the left genome end of bovine herpesvirus.” Veterinary Microbiology. 53: 67-77.
Misra V, Walker S, Yang P, Hayes S, O'Hare P. 1996. “Conformational alteration of Oct-1 upon DNA binding dictates selectivity in differential interactions with related transcriptional coactivators.” Molecular and Cellular Biology. 16: 4404-4413.
Jackson ML, Haines DM, Misra V. 1996. “Sequence analysis of the putative viral enhancer in tissues from 33 cats with various feline leukemia virus related diseases.” Veterinary Microbiology. 53: 213-225.
Jackson ML, Wood SL, Misra V, Haines DM. 1996. “Immunohistochemical identification of B and T lymphocytes in formalin-fixed, paraffin embedded feline lymphosarcomas: relation to feline leukemia virus status, tumor site, and patient age.” Canadian Journal of Veterinary Research. 60: 199-204.
Jackson ML, Haines DM, Taylor SM, Misra V. 1996. “Feline leukaemia virus detection by ELISA in peripheral blood from 68 cats with high, moderate or low suspicion of having FeLV related disease.” Journal of Veterinary Diagnostic Investigation. 8:25-30.
Dr. Marion Jackson's PhD thesis. Co-supervised by Drs. Haines and Misra. Research supported by a grant from the WCVM’s Companion Animal Health Fund.
Misra V, Walker S, Hayes S, O'Hare P. 1995. “The bovine herpesvirus alpha gene trans inducing factor activates transcription by mechanisms different from those of its herpes simplex virus counterpart VP16.” Journal of Virology. 69: 5209-5216.
Lindsell CE, Misra V, Murphy BD. 1995. “Follistatin has characteristics of a primary response gene in porcine granulosa cells.” Endocrine. 3: 609-614.