State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Republic of China.
Australian Animal Health Laboratory, Commonwealth Scientific and Industrial Research Organisation Livestock Industries, Geelong, Victoria, Australia.
J Gen Virol. 2012 Feb;93(Pt 2):275-281. doi: 10.1099/vir.0.033589-0. Epub 2011 Oct 19.
The ORF3b protein of severe acute respiratory syndrome coronavirus (SARS-CoV) has a nuclear localization signal (NLS) at its C terminus and antagonizes interferon (IFN) function by modulating the activity of IFN regulatory factor 3 (IRF3). SARS-like coronaviruses (SL-CoVs) found in bats share an identical genome organization and high sequence identity for most of their gene products. In this study, ORF3b homologues were identified from three bat SL-CoV strains. These ORF3b homologues were C-terminally truncated and lacked the C-terminal NLS of SARS-CoV. IFN antagonist activities analysis demonstrated that one SL-CoV ORF3b still possessed IFN antagonist and IRF3-modulating activities. These results indicate that different ORF3b proteins display different IFN antagonist activities and this function is independent of the protein's nuclear localization, suggesting a potential link between bat SL-CoV ORF3b function and viral pathogenesis.
严重急性呼吸综合征冠状病毒(SARS-CoV)的 ORF3b 蛋白在其 C 末端具有核定位信号(NLS),并通过调节干扰素调节因子 3(IRF3)的活性来拮抗干扰素(IFN)功能。蝙蝠中发现的类似严重急性呼吸综合征冠状病毒(SL-CoVs)具有相同的基因组组织和大多数基因产物的高序列同一性。在这项研究中,从三种蝙蝠 SL-CoV 株中鉴定出了 ORF3b 同源物。这些 ORF3b 同源物在 C 末端截断,并且缺乏 SARS-CoV 的 C 末端 NLS。IFN 拮抗剂活性分析表明,一种 SL-CoV ORF3b 仍然具有 IFN 拮抗剂和 IRF3 调节活性。这些结果表明,不同的 ORF3b 蛋白显示出不同的 IFN 拮抗剂活性,并且该功能独立于蛋白质的核定位,这表明蝙蝠 SL-CoV ORF3b 功能与病毒发病机制之间存在潜在联系。