The innate signaling adaptor MAVS regulates the quality of the antibody response to West Nile Virus

Abstract

Abstract A key difference that distinguishes viral infections from protein immunizations is the recognition of viral nucleic acids by cytosolic pattern recognition receptors (PRRs) during the course of infections. Cytosolic PRRs play a crucial role in the control of innate immunity to many viral infections. In contrast to transmembrane PRRs such as Toll-like receptors, however, the functions of cytosolic PRRs in the regulation of protective adaptive immunity have remained poorly understood. Rig-I-like Receptors (RLRs) are a family of PRRs that recognize microbial RNA in the cytosol and induce cytokine and interferon responses via the essential signaling adaptor MAVS. Infection of MAVS-deficient mice with West Nile Virus (WNV) results in a defective adaptive immune response. While this finding suggests a role for RLRs in the regulation of adaptive immunity to WNV, it is difficult to interpret due to the high WNV viremia and associated antigen loads in the absence of a MAVS-dependent innate immune response. In order to overcome these limitations, we have infected MAVS-deficient mice with a single-round-of-infection mutant of WNV. MAVS-deficient mice failed to produce an effective neutralizing antibody response to WNV despite normal titers of antibodies targeting the neutralizing lateral ridge epitope in the DIII domain of WNV-E protein. Instead, the antibodies of MAVS-deficient mice bound the neutralizing epitope with lower affinity. Our findings suggest that RLR-dependent signals are important for the quality of the humoral immune response to WNV.