PMID- 23845800 OWN - NLM STAT- MEDLINE DCOM- 20140826 LR - 20211021 IS - 1873-2518 (Electronic) IS - 0264-410X (Print) IS - 0264-410X (Linking) VI - 31 IP - 38 DP - 2013 Aug 28 TI - A West Nile virus NS4B-P38G mutant strain induces adaptive immunity via TLR7-MyD88-dependent and independent signaling pathways. PG - 4143-51 LID - S0264-410X(13)00903-1 [pii] LID - 10.1016/j.vaccine.2013.06.093 [doi] AB - 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. CI - Copyright (c) 2013 Elsevier Ltd. All rights reserved. FAU - Xie, Guorui AU - Xie G AD - Department of Microbiology & Immunology, The University of Texas Medical Branch, Galveston, TX 77555, USA. FAU - Welte, Thomas AU - Welte T FAU - Wang, Jia AU - Wang J FAU - Whiteman, Melissa C AU - Whiteman MC FAU - Wicker, Jason A AU - Wicker JA FAU - Saxena, Vandana AU - Saxena V FAU - Cong, Yingzi AU - Cong Y FAU - Barrett, Alan D T AU - Barrett AD FAU - Wang, Tian AU - Wang T LA - eng GR - R01 AI072060/AI/NIAID NIH HHS/United States GR - AI072060/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20130708 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (Cytokines) RN - 0 (Membrane Glycoproteins) RN - 0 (Myd88 protein, mouse) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (Receptors, Interleukin-1) RN - 0 (Tlr7 protein, mouse) RN - 0 (Toll-Like Receptor 7) SB - IM MH - *Adaptive Immunity MH - Amino Acid Sequence MH - Animals MH - Cytokines/metabolism MH - Dendritic Cells/immunology/virology MH - Host-Pathogen Interactions MH - Immunity, Humoral MH - Immunologic Memory MH - Membrane Glycoproteins/genetics/immunology/*metabolism MH - Mice MH - Mice, Mutant Strains MH - Molecular Sequence Data MH - Mutation MH - Myeloid Differentiation Factor 88/genetics/immunology/*metabolism MH - Receptors, Interleukin-1/genetics/metabolism MH - Signal Transduction/immunology MH - T-Lymphocytes/immunology/metabolism/virology MH - Toll-Like Receptor 7/genetics/immunology/*metabolism MH - West Nile virus/*genetics/*immunology/pathogenicity PMC - PMC3870894 MID - NIHMS502830 OTO - NOTNLM OT - B6 OT - BM OT - C57BL/6 OT - CNS OT - DCs OT - E OT - IFN OT - Immune response OT - LD OT - MyD88 OT - NS OT - NS4B protein OT - Q-PCR OT - T cell OT - TLR OT - Toll-like receptor OT - WNV OT - West Nile virus OT - bone marrow OT - central nervous system OT - dendritic cells OT - envelope OT - i.p. OT - interferon OT - intraperitoneally OT - lethal dose OT - myeloid differentiation factor 88 OT - nonstructural OT - quantitative PCR EDAT- 2013/07/13 06:00 MHDA- 2014/08/27 06:00 PMCR- 2014/08/28 CRDT- 2013/07/13 06:00 PHST- 2013/02/14 00:00 [received] PHST- 2013/06/20 00:00 [revised] PHST- 2013/06/25 00:00 [accepted] PHST- 2013/07/13 06:00 [entrez] PHST- 2013/07/13 06:00 [pubmed] PHST- 2014/08/27 06:00 [medline] PHST- 2014/08/28 00:00 [pmc-release] AID - S0264-410X(13)00903-1 [pii] AID - 10.1016/j.vaccine.2013.06.093 [doi] PST - ppublish SO - Vaccine. 2013 Aug 28;31(38):4143-51. doi: 10.1016/j.vaccine.2013.06.093. Epub 2013 Jul 8.