Immune responses to an attenuated West Nile virus NS4B-P38G mutant strain

Thomas Welte, Guorui Xie, Jason A. Wicker, Melissa C. Whitemanb, Li Li, Aparna Rachamallu, Alan Barrett, Tian Wang

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

The nonstructural (NS) proteins of West Nile virus (WNV) have been associated with participation in evasion of host innate immune defenses. In the present study, we characterized immune response to an attenuated WNV strain, which has a P38G substitution in the NS4B protein. The WNV NS4B-P38G mutant induced a lower level of viremia and no lethality in C57BL/6 (B6) mice following a systemic infection. Interestingly, there were higher type 1 IFNs and IL-1β responses compared to mice infected by wild-type WNV. NS4B-P38G mutant-infected mice also showed stronger effector and memory T cell responses. WNV specific antibody responses were not different between mice infected with these two viruses. As a consequence, all mice were protected from a secondary infection with a lethal dose of wild-type WNV following a primary infection with NS4B-P38G mutant. Moreover, NS4B-P38G mutant infection in cultured bone-marrow derived dendritic cells (DCs) were shown to have a reduced replication rate, but a higher level of innate cytokine production than wild-type WNV, some of which were dependent on Myd88 signaling. In conclusion, the NS4B-P38G mutant strain induces higher protective innate and adaptive immune response in mice, which results in a lower viremia and no lethality in either primary or secondary infection, suggesting a high potential as an attenuating mutation in a vaccine candidate.

Original languageEnglish (US)
Pages (from-to)4853-4861
Number of pages9
JournalVaccine
Volume29
Issue number29-30
DOIs
StatePublished - Jun 24 2011

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Keywords

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

ASJC Scopus subject areas

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

Cite this

Welte, T., Xie, G., Wicker, J. A., Whitemanb, M. C., Li, L., Rachamallu, A., Barrett, A., & Wang, T. (2011). Immune responses to an attenuated West Nile virus NS4B-P38G mutant strain. Vaccine, 29(29-30), 4853-4861. https://doi.org/10.1016/j.vaccine.2011.04.057