A West Nile virus NS4B-P38G mutant strain induces adaptive immunity via TLR7-MyD88-dependent and independent signaling pathways.
A West Nile virus NS4B-P38G mutant strain induces adaptive immunity via TLR7-MyD88-dependent and independent signaling pathways.
复制标题
西尼罗河病毒 NS4B-P38G 突变株通过 TLR7-MyD88 依赖性和独立信号通路诱导适应性免疫。
DOI：
10.1016/j.vaccine.2013.06.093
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发表时间：
2013
期刊：
影响因子：
5.5
通讯作者：
Wang,Tian
中科院分区：
文献类型：
--
作者：
Xie,Guorui;Welte,Thomas;Wang,Jia;Whiteman,MelissaC;Wicker,JasonA;Saxena,Vandana;Cong,Yingzi;Barrett,AlanDT;Wang,Tian
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
