The anti-viral and signal-3 effects of Type-I interferons exert opposing effects on clonal expansion of CD8 T cells during West Nile Virus infection (154.13)

Abstract

West Nile Virus (WNV) is a neurotropic positive stranded RNA virus, which affects central nervous system in a fraction of infected humans in several continents, including North America. In concert with innate responses both antibody and T cell mediated immunity play an important role in conferring protection against WNV. While the importance of type-I IFN-I (IFN-I) signaling on WNV-specific innate immunity is well documented, it remains unclear whether and what effects IFN-I have on WNV-specific adaptive response. Using a murine foot pad infection model of WNV infection here we asked two questions: (1) what happens to virus-specific CD8 T cell responses if the infected host is devoid of IFN-I signaling, (2) what happens to virus-specific CD8 response if only CD8 T cells lack IFN-I signaling. We found that lack of IFN-I signaling in the host results in exaggerated CD8 clonal expansion whereas lack of IFN-I signaling exclusively in CD8 T cells results in diminished clonal expansion. Our results together, suggest INF-I mediated innate viral control and the ability to provide signal-3 exerts opposing effects on CD8 T cell expansion during West Nile Virus infection.