MAVS regulates the quality of the antibody response to West-Nile Virus

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Abstract
A key difference that distinguishes viral infections from protein immunizations is the recognition of viral nucleic acids by cytosolic pattern recognition receptors (PRRs) such as RNA-sensing Rig-I-like receptors (RLRs). Insights into the specific functions of cytosolic PRRs in the instruction of adaptive immunity are therefore critical for the understanding of protective immunity to infections. West Nile virus (WNV) infection of mice deficent of MAVS, the essential RLR signaling adaptor, results in a defective adaptive immune response. While this finding suggests a role for RLRs in the instruction of adaptive immunity to WNV, it is difficult to interpret due to the high WNV viremia, associated exessive antigen loads, and pathology in the absence of a MAVS-dependent innate immune response. To overcome these limitations, we have infected MAVS-deficient mice with a single-round-of-infection mutant of WNV called RepliVAX (RWN). RWN-infected MAVS-deficient (MAVS KO ) mice failed to produce an effective neutralizing antibody response to WNV despite normal titers of antibodies targeting the viral WNV-E protein. This defect occurred indepedently of antigen loads or overt pathology. The specificity of the antibody response in RWN-infected MAVS KO mice remained unchanged and was still dominated by antibodies that bound the neutralizing lateral ridge (LR) epitope in the DIII domain of WNV-E. Instead, MAVS KO mice produced IgM antibodies, the dominant isotype controlling primary WNV infection, with lower affinity for the DIII domain. Our findings suggest that RLR-dependent signals are important for the quality of the humoral immune response to WNV.
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