A West Nile virus NS4B-P38G mutant strain induces adaptive immunity via TLR7-MyD88-dependent and independent signaling pathways

Guorui Xie, Thomas Welte, Jia Wang, Melissa C. Whiteman, Jason A. Wicker, Vandana Saxena, Yingzi Cong, Alan D.T. Barrett, Tian Wang

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Prior work shows that an attenuated West Nile virus (WNV), the nonstructural (NS)4B-P38G mutant infection in mice induced strong immune responses and protected host from subsequent lethal wild-type WNV infection. Here, we investigated NS4B-P38G mutant infection in myeloid differentiation factor 88-deficient (MyD88-/-) and Toll-like receptor 7-deficient (TLR7-/-) mice and found they had enhanced susceptibility compared to wild-type mice. Both groups had lower WNV-specific IgM response and reduced effector T cell functions. Dendritic cells (DCs) also exhibited a reduced maturation and impaired antigen-presenting functions compared to wild-type DCs. Moreover, infection with NS4B-P38G mutant in TLR7-/- and MyD88-/- mice provided full and partial protection respectively from subsequent challenge with lethal wild-type WNV. There were reduced T cell responses in MyD88-/- and interleukin-1 receptor deficient (IL-1R-/-) mice during secondary challenge with wild-type WNV. In contrast, TLR7-/- mice displayed normal T cell functions. Collectively, these results suggest that TLR7-dependent MyD88 signaling is required for T cell priming during NS4B-P38G mutant infection, whereas the TLR7-independent MyD88 signaling pathways are involved in memory T cell development, which may contribute to host protection during secondary challenge with wild-type WNV.

Original languageEnglish (US)
Pages (from-to)4143-4151
Number of pages9
JournalVaccine
Volume31
Issue number38
DOIs
StatePublished - Aug 28 2013

Keywords

  • Immune response
  • NS4B protein
  • T cell
  • West Nile virus

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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