MAVS is essential for primary CD4+ T cell immunity but not for recall T cell responses following an attenuated West Nile virus infection

Huanle Luo, Evandro Winkelmann, Guorui Xie, Rong Fang, Bi Hung Peng, Li Li, Helen M. Lazear, Slobodan Paessler, Michael S. Diamond, Michael Gale, Alan D. Barrett, Tian Wang

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


The use of pathogen recognition receptor (PRR) agonists and the molecular mechanisms involved have been the major focus of research in individual vaccine development. West Nile virus (WNV) nonstructural (NS) 4B-P38G mutant has several features for an ideal vaccine candidate, including significantly reduced neuroinvasiveness, induction of strong adaptive immunity, and protection of mice from wild-type (WT) WNV infection. Here, we determined the role of mitochondrial antiviral signaling protein (MAVS), the adaptor protein for RIG-I-like receptor in regulating host immunity against the NS4B-P38G vaccine. We found that Mavs-/- mice were more susceptible to NS4B-P38G priming than WT mice. Mavs-/- mice had a transiently reduced production of antiviral cytokines and an impaired CD4+ T cell response in peripheral organs. However, antibody and CD8+ T cell responses were minimally affected. NS4B-P38G induced lower type I interferon (IFN), IFN-stimulating gene, and proinflammatory cytokine responses in Mavs-/- dendritic cells and subsequently compromised the antigen-presenting capacity for CD4+ T cells. Interestingly, Mavs-/- mice surviving NS4B-P38G priming were all protected from a lethal WT WNV challenge. NS4B-P38G-primed Mavs-/- mice exhibited equivalent levels of protective CD4+ T cell recall response, a modestly reduced WNV-specific IgM production, but more robust CD8+ T cell recall response. Taken together, our results suggest that MAVS is essential for boosting optimal primary CD4+ T cell responses upon NS4B-P38G vaccination and yet is dispensable for host protection and recall T cell responses during secondary WT WNV infection.

Original languageEnglish (US)
Article numbere02097-16
JournalJournal of virology
Issue number6
StatePublished - 2017


  • Adaptive immunity
  • MAVS
  • T cell
  • T cells
  • Vaccine
  • West Nile virus

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology


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