Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Oligoadenylate-Synthetase-Family Protein OASL Inhibits Activity of the DNA Sensor cGAS during DNA Virus Infection to Limit Interferon Production.
Immunity ( IF 25.5 ) Pub Date : 2019-01-08 , DOI: 10.1016/j.immuni.2018.12.013 Arundhati Ghosh 1 , Lulu Shao 1 , Padmavathi Sampath 2 , Baoyu Zhao 3 , Nidhi V Patel 4 , Jianzhong Zhu 1 , Bharat Behl 5 , Robert A Parise 6 , Jan H Beumer 6 , Roderick J O'Sullivan 7 , Neal A DeLuca 1 , Stephen H Thorne 2 , Vijay A K Rathinam 5 , Pingwei Li 3 , Saumendra N Sarkar 1
Immunity ( IF 25.5 ) Pub Date : 2019-01-08 , DOI: 10.1016/j.immuni.2018.12.013 Arundhati Ghosh 1 , Lulu Shao 1 , Padmavathi Sampath 2 , Baoyu Zhao 3 , Nidhi V Patel 4 , Jianzhong Zhu 1 , Bharat Behl 5 , Robert A Parise 6 , Jan H Beumer 6 , Roderick J O'Sullivan 7 , Neal A DeLuca 1 , Stephen H Thorne 2 , Vijay A K Rathinam 5 , Pingwei Li 3 , Saumendra N Sarkar 1
Affiliation
|
Interferon-inducible human oligoadenylate synthetase-like (OASL) and its mouse ortholog, Oasl2, enhance RNA-sensor RIG-I-mediated type I interferon (IFN) induction and inhibit RNA virus replication. Here, we show that OASL and Oasl2 have the opposite effect in the context of DNA virus infection. In Oasl2-/- mice and OASL-deficient human cells, DNA viruses such as vaccinia, herpes simplex, and adenovirus induced increased IFN production, which resulted in reduced virus replication and pathology. Correspondingly, ectopic expression of OASL in human cells inhibited IFN induction through the cGAS-STING DNA-sensing pathway. cGAS was necessary for the reduced DNA virus replication observed in OASL-deficient cells. OASL directly and specifically bound to cGAS independently of double-stranded DNA, resulting in a non-competitive inhibition of the second messenger cyclic GMP-AMP production. Our findings define distinct mechanisms by which OASL differentially regulates host IFN responses during RNA and DNA virus infection and identify OASL as a negative-feedback regulator of cGAS.
中文翻译：
寡腺苷酸合成酶家族蛋白OASL抑制DNA病毒感染期间DNA传感器cGAS的活性，以限制干扰素的产生。
干扰素诱导型人寡腺苷酸合成酶样（OASL）及其小鼠直向同源物Oasl2增强RNA传感器RIG-I介导的I型干扰素（IFN）诱导并抑制RNA病毒复制。在这里，我们显示OASL和Oasl2在DNA病毒感染的情况下具有相反的作用。在Oasl2-/-小鼠和OASL缺陷型人类细胞中，DNA病毒（如牛痘，单纯疱疹和腺病毒）诱导IFN产生增加，从而导致病毒复制和病理减少。相应地，人细胞中OASL的异位表达通过cGAS-STING DNA传感途径抑制了IFN的诱导。对于在OASL缺陷细胞中观察到的DNA病毒复制减少，cGAS是必需的。OASL独立于双链DNA直接且特异性地与cGAS结合，导致非竞争性抑制第二信使环GMP-AMP的产生。我们的发现定义了不同的机制，OASL通过这些机制在RNA和DNA病毒感染期间差异调节宿主IFN反应，并将OASL鉴定为cGAS的负反馈调节剂。
更新日期：2019-01-08
中文翻译：
寡腺苷酸合成酶家族蛋白OASL抑制DNA病毒感染期间DNA传感器cGAS的活性，以限制干扰素的产生。
干扰素诱导型人寡腺苷酸合成酶样（OASL）及其小鼠直向同源物Oasl2增强RNA传感器RIG-I介导的I型干扰素（IFN）诱导并抑制RNA病毒复制。在这里，我们显示OASL和Oasl2在DNA病毒感染的情况下具有相反的作用。在Oasl2-/-小鼠和OASL缺陷型人类细胞中，DNA病毒（如牛痘，单纯疱疹和腺病毒）诱导IFN产生增加，从而导致病毒复制和病理减少。相应地，人细胞中OASL的异位表达通过cGAS-STING DNA传感途径抑制了IFN的诱导。对于在OASL缺陷细胞中观察到的DNA病毒复制减少，cGAS是必需的。OASL独立于双链DNA直接且特异性地与cGAS结合，导致非竞争性抑制第二信使环GMP-AMP的产生。我们的发现定义了不同的机制，OASL通过这些机制在RNA和DNA病毒感染期间差异调节宿主IFN反应，并将OASL鉴定为cGAS的负反馈调节剂。
京公网安备 11010802027423号