In 2015 the Retroviral Immunology Section continued investigation into host mechanisms of genetic resistance and susceptibility to retroviral infection. These findings have implications for the design of therapeutics and vaccines to treat and prevent infections with viruses such as HIV. Studies of Friend retrovirus-infected mice to determine how acute infections are resolved by immune responses elucidated a critical role for CD8+ cytotoxic T cells. In 2015 we investigated the role of regulatory T cells in suppressing CD8+ T cell responses by suppressing the activation of antigen presenting cells including DCs, macrophages and B cells. We found that regulatory T cells exert a potent suppression on the expression of costimulatory molecules on antigen presenting cells. By depleting regulatory T cells we were able to significantly increase antigen presentation functions in vitro and demonstrate potent effects on the CD8+ T cell responses in vivo. In a collaborative study with the Potts lab we studied how a retrovirus (Friend virus or FV) can increase its pathogenicity over time in a population. We demonstrate rapid increases in viral titers and virulence when the virus was used to serially infect a series of inbred mice representing the same genotype, but not when infecting a diverse array of inbred mouse strains. This experiment modeled the diversity in natural host populations. We found that a single infection of a different host genotype was sufficient to constrain the emergence of a high fitness/high virulence phenotype. Results from our experiments provide an important first step in understanding how genetic variation among vertebrate hosts influences pathogen evolution. The results suggest that serial exposure to different genotypes within a single host species may act as a constraint on pathogen adaptation that prohibits the emergence of more virulent infections. From a practical perspective, these results have implications for low-diversity host populations such as endangered species and domestic animals (Kubinak et al. 2015).
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