Late SARS-CoV-2 Infection Events

Stable Identifier
R-HSA-9772573
Type
Pathway
Species
Homo sapiens
Related Species
Severe acute respiratory syndrome coronavirus 2
ReviewStatus
5/5
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Late SARS-CoV-2 Infection Events
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The coronavirus virion consists of structural proteins, namely spike (S), envelope (E), membrane (M), nucleocapsid (N) and, for some betacoronaviruses, haemagglutinin-esterase. The positive-sense, single-stranded RNA genome (+ssRNA) is encapsidated by N, whereas M and E ensure its incorporation in the viral particle during the assembly process. S trimers protrude from the host-derived viral envelope and provide specificity for cellular entry receptors. SARS-CoV-2 particles bind to angiotensin-converting enzyme 2 (ACE2) cellular receptors and together with host factors (such as the cell surface serine protease TMPRSS2), promote viral uptake and fusion at the cellular or endosomal membrane. Following entry, the release and uncoating of the incoming genomic RNA subject it to the immediate translation of two large open reading frames, ORF1a and ORF1b. ORF1a and ORF1b encode 1516 non-structural proteins (nsp), of which 15 compose the viral replication and transcription complex (RTC) that includes, amongst others, RNA-processing and RNA-modifying enzymes and an RNA proofreading function necessary for maintaining the integrity of the >30kb coronavirus genome. ORFs that encode structural proteins and interspersed ORFs that encode accessory proteins are transcribed from the 3' one-third of the genome to form a nested set of subgenomic mRNAs (sg mRNAs). The resulting polyproteins pp1a and pp1ab are co-translationally and post-translationally processed into the individual non-structural proteins (nsps) that form the viral replication and transcription complex. Concordant with the expression of nsps, the biogenesis of viral replication organelles consisting of characteristic perinuclear double-membrane vesicles (DMVs), convoluted membranes (CMs) and small open double-membrane spherules (DMSs) create a protective microenvironment for viral genomic RNA replication and transcription of subgenomic mRNAs comprising the characteristic nested set of coronavirus mRNAs. Translated structural proteins translocate into endoplasmic reticulum (ER) membranes and transit through the ER-to-Golgi intermediate compartment (ERGIC), where interaction with N-encapsidated, newly produced genomic RNA results in budding into the lumen of secretory vesicular compartments. Finally, virions are secreted from the infected cell by exocytosis. A successful intracellular coronavirus life cycle invariably relies on critical molecular interactions with host proteins that are repurposed to support the requirements of the virus. This includes host factors required for virus entry (such as the entry receptor and host cell proteases), factors required for viral RNA synthesis and virus assembly (such as ER and Golgi components and associated vesicular trafficking pathways) and factors required for the translation of viral mRNAs (such as critical translational initiation factors)
Literature References
PubMed ID Title Journal Year
33116300 Coronavirus biology and replication: implications for SARS-CoV-2

V'kovski, P, Kratzel, A, Steiner, S, Stalder, H, Thiel, V

Nat Rev Microbiol 2021
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
Events
Participates
as an event of
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
Cross References
Mondo
Authored
Gillespie, ME  (2022-05-10)
Reviewed
Acencio, ML  (2021-05-09)
Created
Gillespie, ME  (2022-04-22)
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