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PLoS One. 2019 Jun 26;14(6):e0218928. doi: 10.1371/journal.pone.0218928. eCollection 2019.

Dendritic cell-associated MAVS is required to control West Nile virus replication and ensuing humoral immune responses.

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Department of Immunology, University of Washington, Seattle, Washington, United States of America.
Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, Georgia, United States of America.
Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, Georgia, United States of America.
Center for Innate Immunity and Immune Disease, University of Washington, Seattle, Washington, United States of America.


Mitochondrial antiviral signaling protein (MAVS) is a critical innate immune signaling protein that directs the actions of the RIG-I-like receptor (RLR) signaling pathway of RNA virus recognition and initiation of anti-viral immunity against West Nile virus (WNV). In the absence of MAVS, mice die more rapidly after infection with the pathogenic WNV-Texas (TX) strain, but also produce elevated WNV-specific IgG concomitant with increased viral burden. Here we investigated whether there was a B cell intrinsic role for MAVS during the development of protective humoral immunity following WNV infection. MAVS-/- mice survived infection from the non-pathogenic WNV-Madagascar (MAD) strain, with limited signs of disease. Compared to wildtype (WT) controls, WNV-MAD-infected MAVS-/- mice had elevated serum neutralizing antibodies, splenic germinal center B cells, plasma cells and effector T cells. We found that when rechallenged with the normally lethal WNV-TX, MAVS-/- mice previously infected with WNV-MAD were protected from disease. Thus, protective humoral and cellular immune responses can be generated in absence of MAVS. Mice with a conditional deletion of MAVS only in CD11c+ dendritic cells phenocopied MAVS whole body knockout mice in their humoral responses to WNV-MAD, displaying elevated virus titers and neutralizing antibodies. Conversely, a B cell-specific deletion of MAVS had no effect on immune responses to WNV-MAD compared to WT controls. Thus, MAVS in dendritic cells is required to control WNV replication and thereby regulate downstream humoral immune responses.

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