Elsevier

Virology

Volume 517, April 2018, Pages 3-8
Virology

Physiological and molecular triggers for SARS-CoV membrane fusion and entry into host cells

https://doi.org/10.1016/j.virol.2017.12.015Get rights and content
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Highlights

  • SARS-CoV as model for studying the coronavirus (CoV) fusion peptide (FP).

  • Evidence based on functional and biophysical analyses that reveal the region downstream of the coronavirus spike protein S2′ cleavage as the bona fide FP that forms an extended “fusion platform”.

  • Evidence for a direct role for calcium cations in mediating membrane fusion of SARS-CoV.

  • Unusual features of the CoV FP that set it apart from other class I fusion peptides.

  • The biphasic nature of SARS-CoV cellular entry pathways can be explained by calcium-dependency of fusion.

Abstract

During viral entry, enveloped viruses require the fusion of their lipid envelope with host cell membranes. For coronaviruses, this critical step is governed by the virally-encoded spike (S) protein, a class I viral fusion protein that has several unique features. Coronavirus entry is unusual in that it is often biphasic in nature, and can occur at or near the cell surface or in late endosomes. Recent advances in structural, biochemical and molecular biology of the coronavirus S protein has shed light on the intricacies of coronavirus entry, in particular the molecular triggers of coronavirus S-mediated membrane fusion. Furthermore, characterization of the coronavirus fusion peptide (FP), the segment of the fusion protein that inserts to a target lipid bilayer during membrane fusion, has revealed its particular attributes which imparts some of the unusual properties of the S protein, such as Ca2+-dependency. These unusual characteristics can explain at least in part the biphasic nature of coronavirus entry. In this review, using severe acute respiratory syndrome coronavirus (SARS-CoV) as model virus, we give an overview of advances in research on the coronavirus fusion peptide with an emphasis on its role and properties within the biological context of host cell entry.

Keywords

Coronavirus
SARS
Spike protein
Virus entry
Endosomes
Calcium
Fusion peptide

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