人类冠状病毒调节宿主抗病毒天然免疫分子机制

Regulation of Antiviral Innate Immune Responses by Human Coronavirus

SARS冠状病毒和正在全球流行的猪源H1N1型流感病毒等人类新发呼吸道病毒对人类生命健康构成严重威胁.人类重要呼吸道病毒与宿主抗病毒天然免疫的关系是近年来研究热点.SARS冠状病毒等很多RNA病毒能够编码某种蛋白质,抑制干扰素表达以及干扰素介导的抗病毒信号通路.人类冠状病毒木瓜样蛋白酶(papain-like protease,PLP)利用其自身去泛素化酶(DUB)活性,使干扰素表达通路中重要调节蛋白发生去泛素化,从而抑制干扰素信号传导.同时,PLP蛋白酶通过阻碍干扰素表达信号通路中最新发现的重要调节蛋白ERIS(也称MITA/STING)二聚化,使其失活并丧失激活干扰素通路的功能,这些发现对于阐明人类重要呼吸道病毒对宿主细胞抗病毒天然免疫反应的调节作用及其机制具有重要意义,为人类新发病毒致病机理、免疫防治以及抗病毒药物研究提供新的思路.

Emerging and re-emerging human viral pathogens, such as severe acute respiratory syndrome （SARS）, which emerged in 2003, and the recently emerged swine-origin H1N1 influenza virus, which causes global pandemics, have had a worldwide impact and therefore represent a serious threat to human health. Viruses as the obligate parasites strictly depend on host cells for replication and, throughout co-evolution with hosts, viruses have developed strategies to evade and subvert the host antiviral innate immune response. A wide variety of RNA viruses have been reported to encode proteins that inhibit host innate immune responses. Papain-like protease （PLP） of human coronavirus is a novel viral-encoded deubiquitinase and is an IFN antagonist for inhibition of host antiviral innate immune response through disruption of ERIS （also called MITA/STING）-mediated signaling. The novel mechanisms by which human coronavirus inhibits host IFN response and new findings that papain-like protease （PLP） of coronavirus is an IFN antagonist which targets specific components of the IFN induction pathway were introduced.