Murine retroviruses activate B cells via interaction with toll-like receptor 4
Murine retroviruses activate B cells via interaction with toll-like receptor 4
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DOI：
10.1073/pnas.042355399
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发表时间：
2002-02-19
影响因子：
11.1
通讯作者：
Ross, SR
中科院分区：
文献类型：
--
作者：
Rassa, JC;Meyers, JL;Ross, SR
虽然大多数逆转录病毒需要活化的细胞作为其感染的靶点，但尚不清楚这是如何在体内实现的。小鼠乳腺肿瘤病毒（MMTV）或鼠白血病病毒激活B细胞的候选蛋白质是toll样受体4（TLR 4），其是先天免疫系统的组分。MMTV在C3 H/HeN小鼠中引起B细胞活化，但在C3 H/HeJ或BALB/c（C.C3 H Tlr 4（lps-d））同源小鼠中不引起，这两种小鼠都具有突变的TLR 4基因。这种激活与病毒基因表达无关，因为它发生在用紫外线或2，2 '-二硫代二吡啶处理MMTV后以及叠氮胸苷处理的小鼠中。从MMTV注射的C3 H/HeN而不是C3 H/HeJ小鼠的淋巴细胞制备的核提取物显示核因子kappaB活性增加。此外，MMTV和莫洛尼鼠白血病病毒包膜蛋白与TLR 4在293 T细胞中表达时共免疫沉淀。MMTV受体未能与TLR 4共免疫沉淀，表明MMTV/TLR 4相互作用不依赖于病毒附着和融合。这些结果确定了与哺乳动物Toll受体相互作用的逆转录病毒蛋白，并表明这些病毒的直接激活可能会启动体内感染途径。
Although most retroviruses require activated cells as their targets for infection, it is not known how this is achieved in vivo. A candidate protein for the activation of B cells by either mouse mammary tumor virus (MMTV) or murine leukemia virus is the toll-like receptor 4 (TLR4), a component of the innate immune system. MMTV caused B cell activation in C3H/HeN mice but not in C3H/HeJ or BALB/c (C.C3H Tlr4(lps-d)) congenic mice, both of which have a mutant TLR4 gene. This activation was independent of viral gene expression, because it occurred after treatment of MMTV with ultraviolet light or 2,2'-dithiodipyridine and in azidothymidine-treated mice. Nuclear extracts prepared from the lymphocytes of MMTV-injected C3H/HeN but not C3H/HeJ mice showed increased nuclear factor kappaB activity. Additionally, the MMTV- and Moloney murine leukemia virus envelope proteins coimmunoprecipitated with TLR4 when expressed in 293T cells. The MMTV receptor failed to coimmunoprecipitate with TLR4, suggesting that MMTV/TLR4 interaction is independent of virus attachment and fusion. These results identify retroviral proteins that interact with a mammalian toll receptor and show that direct activation by such viruses may initiate in vivo infection pathways.