SARS-CoV-2 Infection

Stable Identifier
R-HSA-9694516
DOI
10.3180/R-HSA-9694516.1
Type
Pathway
Species
Homo sapiens
Related Species
Severe acute respiratory syndrome coronavirus 2
ReviewStatus
5/5
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SARS-CoV-2 Infection
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This pathway, SARS-CoV-2 infection of human cells (COVID-19), was initially generated via electronic inference from the manually curated and reviewed Reactome SARS-CoV-1 (Human SARS coronavirus) infection pathway. The inference process created SARS-CoV-2 events corresponding to each event in the SARS-CoV-1 pathway and populated those events with SARS-CoV-2 protein-containing physical entities based on orthology to SARS-CoV-1 proteins (https://reactome.org/documentation/inferred-events). All of these computationally created events and entities have been reviewed by Reactome curators and modified as appropriate where recently published experimental data indicate the existences of differences between the molecular details of the SARS-CoV-1 and SARS-CoV-2 infection pathways.

SARS‑CoV‑2 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 (Hartenian et al. 2020; Fung & Liu 2019; Masters 2006).

This Reactome module also describes molecular mechanisms by which SARS-CoV-2 modulates innate and adaptive immune responses, autophagy, host translation, intracellular signaling and regulatory pathways, and PDZ-mediated cell-cell junctions, mostly annotated from studies of cells infected with SARS-CoV-2.

Literature References
PubMed ID Title Journal Year
12730501 The Genome sequence of the SARS-associated coronavirus

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

Science 2003
31226023 Human Coronavirus: Host-Pathogen Interaction

Fung, TS, Liu, DX

Annu. Rev. Microbiol. 2019
Participants
Events
Participates
as an event of
Inferred From
SARS-CoV-1 Infection (Homo sapiens)
Disease
Name Identifier Synonyms
COVID-19 DOID:0080600 2019 Novel Coronavirus (2019-nCoV), Wuhan seafood market pneumonia virus infection, 2019-nCoV infection, Wuhan coronavirus infection
Authored
Varusai, TM  (2020-06-15)
Haw, R  (2020-09-10)
D'Eustachio, P  (2020-07-22)
Jassal, B  (2020-07-13)
Senff-Ribeiro, A  (2020-08-12)
Orlic-Milacic, M  (2020-07-28)
Stephan, R  (2020-07-22)
Rothfels, K  (2020-07-30)
Gillespie, ME  (2020-08-14)
Reviewed
Acencio, ML  (2020-09-09)
Created
Cook, J  (2020-07-07)
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