Cell intrinsic role for MAVS in regulating CD8 T cell fitness during acute virus infection (P6113)

Abstract

Abstract Mitochondrial antiviral Signaling molecule (MAVS) has been described in it’s role as an adaptor molecule that links viral RNA sensing by RIG-I-like receptors (RLR)s to type I IFN and inflammatory cytokine production. However it’s role in adaptive immune responses to viruses is not well defined. Using an adoptive cell transfer system we examined the requirement for MAVS directly in CD8 T cells during adaptive responses following acute Lymphocytic choriomeningitis virus (LCMV) infection. Here, we found that MAVS plays an RLR-independent role in determining CD8 effector T cell fitness. MAVS-deficient cells were deficient in virus-induced expansion and cytokine production. This deficiency correlated with altered cell size and granularity, differential mitochondrial membrane potential and reduced levels of steady-state intracellular calcium. We found cytokine production deficiencies were acute at earlier stages of CD8 cell expansion, suggesting that the requirement for MAVS is most critical when cellular need for mitochondrial metabolism is maximal. These results suggest that MAVS is required for metabolic support of CD8 effector cell expansion during acute virus infection. Our study therefore assigns a novel metabolic role to MAVS in adaptive CD8 T cell energetics. Defining the function of MAVS in enhancing T cell metabolism therefore has implications for vaccine strategies that aim to increase the quality and quality of the CD8 T cell response to virus infection.