近期，國際病毒學(xué)核心刊物Journal of Virology在線刊登了中科院武漢病毒研究所鄭春福研究員學(xué)科組的研究論文“HSV-1 Tegument Protein US11 down-modulates RLR Signaling Pathway via Direct Interaction with RIG-I and MDA-5,，”,，文章中，研究者介紹了該學(xué)科組在I型單純皰疹病毒拮抗宿主天然免疫反應(yīng)機制研究中取得的新進(jìn)展,。
天然免疫系統(tǒng)是宿主抵抗病毒入侵的第一道防線，I型單純皰疹病毒(HSV-1)已經(jīng)進(jìn)化出多種策略逃逸宿主天然免疫，從而形成裂解感染導(dǎo)致口腔皰疹,、嚴(yán)重的腦炎死亡等疾病，以及終生潛伏感染,。然而,，HSV-1逃逸宿主天然免疫的具體機制還未完全闡明。
在鄭春福研究員的指導(dǎo)下,，博士生邢俊吉等研究首次發(fā)現(xiàn),，HSV-1皮層蛋白US11能夠抑制β干擾素的產(chǎn)生，是一個新的拮抗RIG-I樣模式識別受體（RLR）介導(dǎo)的天然免疫信號通路的HSV-1蛋白。研究人員通過熒光素酶雙報告系統(tǒng)和免疫共沉淀等多種實驗方法,，最終闡明其作用的分子機制為：US11蛋白通過與內(nèi)源性模式識別受體RIG-I和MDA-5相互作用,，干擾它們與接頭蛋白MAVS的相互作用，從而抑制RLR介導(dǎo)的天然免疫下游信號通路IRF3的激活,，阻止β干擾素的產(chǎn)生,。
這是第一次報道HSV-1能干擾RLR信號通路下游的RIG-I和MDA-5。這些發(fā)現(xiàn)揭示了HSV-1逃逸宿主抗病毒應(yīng)答的一種全新的機制,，為預(yù)防HSV-1感染以及揭示新的藥物作用靶點提供了理論依據(jù),。
該研究得到了國家973計劃、國家自然科學(xué)基金和百人計劃的資助,。（生物谷Bioon.com）
doi:10.1128/JVI.06713-11
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HSV-1 Tegument Protein US11 down-modulates RLR Signaling Pathway via Direct Interaction with RIG-I and MDA-5
Junji Xing1, Shuai Wang1, Rongtuan Lin2, Karen L. Mossman3 and Chunfu Zheng1,*
The interferon (IFN)-mediated antiviral response is a major defense of the host immune system. In order to complete their life cycle, viruses must modulate host IFN-mediated immune responses. Herpes simplex virus 1 (HSV-1) is a large DNA virus containing over 80 genes, many of which encode proteins that are involved in virus-host interactions and show immune modulatory capabilities. In this study, we demonstrate that the US11 protein, an RNA binding tegument protein of HSV-1, is a novel antagonism of the IFN-β pathway. US11 significantly inhibited Sendai virus (SeV)-induced IFN-β production, and its dsRNA binding domain was indispensable for this inhibition activity. Additionally, wild type HSV-1 co-infection showed stronger inhibition than US11-mutant HSV-1 in SeV-induced IFN-β production. Co-immunoprecipitation analysis demonstrated that the US11 protein in HSV-1 infected cells interacts with endogenous RIG-I and MDA-5 through its C-terminal RNA-binding domain, which was RNA-independent. Expression of US11 in both transfected and HSV-1 infected cells interferes with the interaction between MAVS and RIG-I or MDA-5. Finally, US11 dampens SeV-mediated IRF3 activation. Taken together, the combined data indicate that HSV-1 US11 binds to RIG-I and MDA-5 and inhibits their downstream signaling pathway, preventing the production of IFN-β, which may contribute to the pathogenesis of HSV-1 infection.
