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

• Type of Material: Article
• Authors: Kelsey Roe, University of Washington; Daniela Giordano, University of Washington; Lucy B. Young, University of Washington; Kevin E. Draves, University of Washington; Ursula Holder, University of Washington; Mehul Suthar, Emory University; Mehul Gale, University of Washington; Edward A. Clark, University of Washington
• Language: English
• Date: 2019-01-01
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2019 Roe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0218928
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 14
• Issue: 6
• Start Page: e0218928
• End Page: e0218928
• Grant/Funding Information: AI83019 and AI52203 awarded to EAC and AI104002 and AI100625 awarded to MG.; This research was supported by the Cell and Analysis Flow Cytometry and Imaging Core in the Department of Immunology at the University of Washington.; This work was supported by grants from the National Institutes of Health (https://www.nih.gov/).
• Research Categories: Health Sciences, Public Health; Health Sciences, Immunology

Abstract

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.