IFN-γ exerts antiviral activity against polyomavirus infection (42.14)

Abstract

Abstract CD8 T cells use both cytolytic and noncytolytic effector mechanisms to eliminate infectious pathogens. Using the mouse polyoma virus (MPyV) system, we have previously shown that TNFa, Fas/FasL, and the perforin/granzyme pathways are dispensable for viral control and susceptibility to MPyV-induced tumors. Here, we investigated whether IFN-γ may be an important effector mechanism for limiting viral burden and tumorigenesis. Using Western analyses for early region nonstructural viral T antigens, as well as FACS analyses of cells infected by a novel recombinant MPyV carrying an intra-T antigen HA epitope tag, we found that IFN-γ reduces expression of viral T antigens in a dose-dependent fashion. Compared to MPyV-infected wild type C57BL/6 mice, IFN-γ receptor KO mice had a 1-log higher viral load during acute infection in most organs, as well as during the persistent phase of MPyV infection; notably, 3-log higher viral genome copies were present in the kidneys, a major site of persistence by both murine and human polyomaviruses. This increase in viral burden was not due to a lack of responding cells, as fully functional virus-specific CD8 T cells were found during the entire course of infection in IFN-γR KO mice at levels similar to those seen in wild type mice. Studies are underway to determine if IFN-γ receptor KO mice are susceptible to PyV tumorigenesis and to investigate the importance of IFN-γ as a critical CD8 antiviral effector function in MPyV infection.