SARS-CoV-1 Infection

The SARS-CoV-1 coronavirus is the causative agent of the outbreak of severe acute respiratory syndrome in 2003 that caused 8,098 known cases of the disease and 774 deaths. The molecular events involved in viral infection and the response of the human host to it have since been studied in detail and are annotated here (de Wit et al. 2016; Marra et al. 2003). The SARS-CoV-1 viral infection pathway here uses entries listed in the UniProt "Human SARS coronavirus (SARS-CoV) (Severe acute respiratory syndrome coronavirus)" taxonomy.<br><br>SARS-CoV-1 infection begins with the binding of viral S (spike) protein to cell surface angiotensin converting enzyme 2 (ACE2) and endocytosis of the bound virion. Within the endocytic vesicle, host proteases mediate cleavage of S protein into S1 and S2 fragments, leading to S2-mediated fusion of the viral and host endosome membranes and release of the viral capsid into the host cell cytosol. The capsid is uncoated to free the viral genomic RNA, whose cap-dependent translation produces polyprotein pp1a and, by means of a 1-base frameshift, polyprotein pp1ab. Autoproteolytic cleavage of pp1a and pp1ab generates 15 or 16 nonstructural proteins (nsps) with various functions. Importantly, the RNA dependent RNA polymerase (RdRP) activity is encoded in nsp12. Nsp3, 4, and 6 induce rearrangement of the cellular endoplasmic reticulum membrane to form cytosolic double membrane vesicles (DMVs) where the viral replication transcription complex is assembled and anchored. With viral genomic RNA as a template, viral replicase-transcriptase synthesizes a full length negative sense antigenome, which in turn serves as a template for the synthesis of new genomic RNA. The replicase-transcriptase can also switch template during discontinuous transcription of the genome at transcription regulated sequences to produce a nested set of negative-sense subgenomic (sg) RNAs, which are used as templates for the synthesis of positive-sense sgRNAs that are translated to generate viral proteins. Finally, viral particle assembly occurs in the ER Golgi intermediate compartment (ERGIC). Viral M protein provides the scaffold for virion morphogenesis (Fung & Liu 2019; Masters 2006).

SARS-CoV-1冠状病毒是2003年严重急性呼吸综合征大流行的致病因素，该疫情导致8,098例已知病例和774人死亡。自那时起，病毒感染过程中涉及的分子事件以及人类宿主对病毒的响应已被详细研究，并在此处进行了注释（de Wit等，2016年；Marra等，2003年）。本处所述的SARS-CoV-1病毒感染途径采用了UniProt“人类SARS冠状病毒（SARS-CoV）——严重急性呼吸综合征冠状病毒”分类学中的条目。《SARS-CoV-1感染始于病毒S（刺突）蛋白与细胞表面血管紧张素转换酶2（ACE2）的结合，以及结合病毒的吞入。在吞入的囊泡内，宿主蛋白酶介导S蛋白裂解成S1和S2片段，导致S2介导的病毒和宿主内质网膜融合，病毒衣壳释放至宿主细胞质中。衣壳去壳后释放出病毒基因组RNA，其帽依赖性翻译产生多聚蛋白pp1a，并通过1个碱基的移码产生多聚蛋白pp1ab。pp1a和pp1ab的自动裂解产生15或16种具有不同功能的非结构蛋白（nsps）。重要的是，RNA依赖性RNA聚合酶（RdRP）活性编码在ns12中。ns3、4和6诱导细胞内质网膜重排，形成细胞质双层膜囊泡（DMVs），其中病毒复制转录复合体组装并锚定。以病毒基因组RNA为模板，病毒复制转录酶合成全长的负链抗原组，该抗原组随后作为新基因组RNA合成的模板。复制转录酶还可以在基因组转录调控序列的不连续转录过程中切换模板，产生一系列嵌套的负链亚基因组（sg）RNA，这些sgRNA被用作合成正链sgRNA的模板，翻译产生病毒蛋白。最后，病毒颗粒在粗面内质网高尔基中间分室（ERGIC）中组装。病毒M蛋白提供病毒形态发生的基础（Fung & Liu，2019年；Masters，2006年）。”}