Coronavirus Biology and Replication: Implications for SARS-CoV-2

Overview

Journal Nat Rev Microbiol

Specialties Infectious Diseases
Microbiology

Date 2020 Oct 29

PMID 33116300

Citations 1544

Authors

Philip Vkovski

Annika Kratzel

Silvio Steiner

Hanspeter Stalder

Volker Thiel

Affiliations

Soon will be listed here.

Abstract

The SARS-CoV-2 pandemic and its unprecedented global societal and economic disruptive impact has marked the third zoonotic introduction of a highly pathogenic coronavirus into the human population. Although the previous coronavirus SARS-CoV and MERS-CoV epidemics raised awareness of the need for clinically available therapeutic or preventive interventions, to date, no treatments with proven efficacy are available. The development of effective intervention strategies relies on the knowledge of molecular and cellular mechanisms of coronavirus infections, which highlights the significance of studying virus-host interactions at the molecular level to identify targets for antiviral intervention and to elucidate critical viral and host determinants that are decisive for the development of severe disease. In this Review, we summarize the first discoveries that shape our current understanding of SARS-CoV-2 infection throughout the intracellular viral life cycle and relate that to our knowledge of coronavirus biology. The elucidation of similarities and differences between SARS-CoV-2 and other coronaviruses will support future preparedness and strategies to combat coronavirus infections.

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References

Sola I, Almazan F, Zuniga S, Enjuanes L . Continuous and Discontinuous RNA Synthesis in Coronaviruses. Annu Rev Virol. 2016; 2(1):265-88. PMC: 6025776. DOI: 10.1146/annurev-virology-100114-055218. View

Di H, McIntyre A, Brinton M . New insights about the regulation of Nidovirus subgenomic mRNA synthesis. Virology. 2018; 517:38-43. PMC: 5987246. DOI: 10.1016/j.virol.2018.01.026. View

Thiel V, Herold J, Schelle B, Siddell S . Infectious RNA transcribed in vitro from a cDNA copy of the human coronavirus genome cloned in vaccinia virus. J Gen Virol. 2001; 82(Pt 6):1273-1281. DOI: 10.1099/0022-1317-82-6-1273. View

Zhou P, Yang X, Wang X, Hu B, Zhang L, Zhang W . A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020; 579(7798):270-273. PMC: 7095418. DOI: 10.1038/s41586-020-2012-7. View

Hui K, Cheung M, Perera R, Ng K, Bui C, Ho J . Tropism, replication competence, and innate immune responses of the coronavirus SARS-CoV-2 in human respiratory tract and conjunctiva: an analysis in ex-vivo and in-vitro cultures. Lancet Respir Med. 2020; 8(7):687-695. PMC: 7252187. DOI: 10.1016/S2213-2600(20)30193-4. View

Sawicki S, Sawicki D . Coronaviruses use discontinuous extension for synthesis of subgenome-length negative strands. Adv Exp Med Biol. 1995; 380:499-506. DOI: 10.1007/978-1-4615-1899-0_79. View

Liu D, Fung T, Chong K, Shukla A, Hilgenfeld R . Accessory proteins of SARS-CoV and other coronaviruses. Antiviral Res. 2014; 109:97-109. PMC: 7113789. DOI: 10.1016/j.antiviral.2014.06.013. View

Leung G, Hedley A, Ho L, Chau P, Wong I, Thach T . The epidemiology of severe acute respiratory syndrome in the 2003 Hong Kong epidemic: an analysis of all 1755 patients. Ann Intern Med. 2004; 141(9):662-73. DOI: 10.7326/0003-4819-141-9-200411020-00006. View

Ksiazek T, Erdman D, Goldsmith C, Zaki S, Peret T, Emery S . A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med. 2003; 348(20):1953-66. DOI: 10.1056/NEJMoa030781. View

10.

Maier H, Hawes P, Cottam E, Mantell J, Verkade P, Monaghan P . Infectious bronchitis virus generates spherules from zippered endoplasmic reticulum membranes. mBio. 2013; 4(5):e00801-13. PMC: 3812713. DOI: 10.1128/mBio.00801-13. View

11.

Muth D, Corman V, Roth H, Binger T, Dijkman R, Gottula L . Attenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmission. Sci Rep. 2018; 8(1):15177. PMC: 6181990. DOI: 10.1038/s41598-018-33487-8. View

12.

Pfaender S, Mar K, Michailidis E, Kratzel A, Boys I, Vkovski P . LY6E impairs coronavirus fusion and confers immune control of viral disease. Nat Microbiol. 2020; 5(11):1330-1339. PMC: 7916999. DOI: 10.1038/s41564-020-0769-y. View

13.

Ulasli M, Verheije M, de Haan C, Reggiori F . Qualitative and quantitative ultrastructural analysis of the membrane rearrangements induced by coronavirus. Cell Microbiol. 2010; 12(6):844-61. PMC: 7159092. DOI: 10.1111/j.1462-5822.2010.01437.x. View

14.

Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C . Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020; 8(4):420-422. PMC: 7164771. DOI: 10.1016/S2213-2600(20)30076-X. View

15.

Channappanavar R, Fehr A, Vijay R, Mack M, Zhao J, Meyerholz D . Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice. Cell Host Microbe. 2016; 19(2):181-93. PMC: 4752723. DOI: 10.1016/j.chom.2016.01.007. View

16.

Deng X, Hackbart M, Mettelman R, OBrien A, Mielech A, Yi G . Coronavirus nonstructural protein 15 mediates evasion of dsRNA sensors and limits apoptosis in macrophages. Proc Natl Acad Sci U S A. 2017; 114(21):E4251-E4260. PMC: 5448190. DOI: 10.1073/pnas.1618310114. View

17.

Cao Y, Su B, Guo X, Sun W, Deng Y, Bao L . Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients' B Cells. Cell. 2020; 182(1):73-84.e16. PMC: 7231725. DOI: 10.1016/j.cell.2020.05.025. View

18.

Pinto D, Park Y, Beltramello M, Walls A, Tortorici M, Bianchi S . Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Nature. 2020; 583(7815):290-295. DOI: 10.1038/s41586-020-2349-y. View

19.

Woolsey C, Borisevich V, Prasad A, Agans K, Deer D, Dobias N . Establishment of an African green monkey model for COVID-19 and protection against re-infection. Nat Immunol. 2020; 22(1):86-98. PMC: 7790436. DOI: 10.1038/s41590-020-00835-8. View

20.

Hoffmann M, Kleine-Weber H, Pohlmann S . A Multibasic Cleavage Site in the Spike Protein of SARS-CoV-2 Is Essential for Infection of Human Lung Cells. Mol Cell. 2020; 78(4):779-784.e5. PMC: 7194065. DOI: 10.1016/j.molcel.2020.04.022. View