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Vythegi Srithayakumar
Interactions between hosts and pathogens play a crucial role in their adaptation, evolution and persistence. The objective of my thesis is to investigate the immune response elicited by the host in the event of such interaction. The raccoon strain of the rabies virus and its vectors will be used as a model system to study this interaction in wildlife. Raccoon rabies virus (RRV) is a wildlife disease endemic to North America that causes acute encephalopathies in mammals. RRV is commonly regarded as 100% lethal if untreated, thereby limiting the potential for evolutionary adaptation. However, variable immune responses to RRV have been noted, with 5-40% of raccoons surviving clinical RRV challenges. The role of immunologically important MHC DRB alleles will be investigated by characterizing RRV positive and RRV negative raccoons from the eastern periphery of North America. The functional relevance of this gene will be evaluated by examining if there is a non-random association between specific MHC DRB alleles and disease outcome in challenge study and wild samples. As trans-species polymorphism is known to maintain similar MHC alleles among species, an analogous study to that of raccoons will be conducted in skunks. Interspecific response to RRV will be investigated to determine if similar MHC DRB alleles are being selected in the sympatric vectors. This would not only provide insight into the variability in host susceptibility and mechanisms of disease transmission, but also offer novel insight into the evolution of MHC in RRV vectors. To further understand the mechanisms of disease spread, a more in depth analysis of the innate immune response to RRV in raccoons will be carried out by measuring key transcripts indicative of innate defense in the host to rabies. Overall this research would provide a better understanding of the immunological factors that contribute to the pathogenesis of this disease.
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