Rig-I-Like Receptors (RLRs) regulate humoral immunity to West Nile Virus (WNV) infection.

Abstract

Abstract Rig-I-like Receptors (RLRs) comprise a family of pattern recognition receptors that recognizes microbial RNA in the cytosol. RLR activation induces an anti-viral state in infected cells and leads to the release of proinflammatory cytokines and interferons. RLRs are therefore important mediators of innate immunity to many viral infections. However, the role of RLRs in the regulation of adaptive immunity is still poorly understood. Infection of MAVS-deficient mice, the essential signaling adaptor for RLRs, 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 a high WNV viremia in the absence of a MAVS-dependent innate immune response. In order to overcome this caveat, we have infected MAVS-deficient mice with a mutant form of WNV that is unable to assemble infectious virions and is therefore limited to a single round of infection. Here, we show that MAVS-deficient mice display increased numbers of antigen-specific CD4 T cells as well as an enlarged germinal center (GC) B cell compartment. Importantly, these mice fail to produce an effective neutralizing antibody response to WNV despite normal levels of WNV-specific antibodies. Together, these findings suggest that RLR-dependent signals regulate humoral immunity to WNV.