SARS-CoV-1 Infection

Stable Identifier
R-HSA-9678108
Type
Pathway
Species
Homo sapiens
Related Species
Human SARS coronavirus
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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.

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).

Literature References
PubMed ID Title Journal Year
31226023 Human Coronavirus: Host-Pathogen Interaction

Fung, TS, Liu, DX

Annu. Rev. Microbiol. 2019
12730501 The Genome sequence of the SARS-associated coronavirus

Marra, MA, Jones, SJ, Astell, CR, Holt, RA, Brooks-Wilson, A, Butterfield, YS, Khattra, J, Asano, JK, Barber, SA, Chan, SY, Cloutier, A, Coughlin, SM, Freeman, D, Girn, N, Griffith, OL, Leach, SR, Mayo, M, McDonald, H, Montgomery, SB, Pandoh, PK, Petrescu, AS, Robertson, AG, Schein, JE, Siddiqui, A, Smailus, DE, Stott, JM, Yang, GS, Plummer, F, Andonov, A, Artsob, H, Bastien, N, Bernard, K, Booth, TF, Bowness, D, Czub, M, Drebot, M, Fernando, L, Flick, R, Garbutt, M, Gray, M, Grolla, A, Jones, S, Feldmann, H, Meyers, A, Kabani, A, Li, Y, Normand, S, Stroher, U, Tipples, GA, Tyler, S, Vogrig, R, Ward, D, Watson, B, Brunham, RC, Krajden, M, Petric, M, Skowronski, DM, Upton, C, Roper, RL

Science 2003
Participants
Participant Of
Disease
Name Identifier Synonyms
severe acute respiratory syndrome 2945 SARS-CoV infection, SARS
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Reviewed
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