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

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• 作者：Guorui Xie ; Thomas Welte ; Jia Wang ; Melissa C. Whiteman ; Jason A. Wicker ; V ; ana Saxena ; Yingzi Cong ; Alan D.T. Barrett ; Tian Wang
• 关键词：B6 ; C57BL/6 ; BM ; bone marrow ; CNS ; central nervous system ; DCs ; dendritic cells ; E ; envelope ; IFN ; interferon ; i.p. ; intraperitoneally ; LD ; lethal dose ; MyD88 ; myeloid differentiation factor 88 ; NS ; nonstructural ; Q-PCR ; quantitative PCR ; TLR ; Toll-like r
• 刊名：Vaccine
• 出版年：2013
• 出版时间：28 August, 2013
• 年：2013
• 卷：31
• 期：38
• 页码：4143-4151
• 全文大小：1785 K

文摘

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