Ready, Set, Fuse! The Coronavirus Spike Protein and Acquisition of Fusion Competence 英文参考文献.docVIP

Viruses 2012, 4, 557-580; doi:10.3390/v4040557 OPEN ACCESS viruses ISSN 1999-4915 /journal/viruses Review Ready, Set, Fuse! The Coronavirus Spike Protein and Acquisition of Fusion Competence Taylor Heald-Sargent and Tom Gallagher * Department of Microbiology and Immunology, Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153, USA; E-Mail: theald@ * Author to whom correspondence should be addressed; E-Mail: tgallag@; Tel.: +1-708-216-4850. Received: 15 March 2012; in revised form: 29 March 2012 / Accepted: 2 April 2012 / Published: 12 April 2012 Abstract: Coronavirus-cell entry programs involve virus-cell membrane fusions mediated by viral spike (S) proteins. Coronavirus S proteins acquire membrane fusion competence by receptor interactions, proteolysis, and acidification in endosomes. This review describes our current understanding of the S proteins, their interactions with and their responses to these entry triggers. We focus on receptors and proteases in prompting entry and highlight the type II transmembrane serine proteases (TTSPs) known to activate several virus fusion proteins. These and other proteases are essential cofactors permitting coronavirus infection, conceivably being in proximity to cell-surface receptors and thus poised to split entering spike proteins into the fragments that refold to mediate membrane fusion. The review concludes by noting how understanding of coronavirus entry informs antiviral therapies. Keywords: coronavirus; virus entry; viral pathogenesis; spike protein; carcinoembryonic antigen; angiotensin converting enzyme 2; endocytosis; cathepsin; transmembrane protease; membrane fusion 1. Introduction Coronaviruses (CoVs) are enveloped RNA viruses causing respiratory and enteric diseases. The CoVs are widely distributed in nature and their zoonotic transmissions into human populations can cause epidemic disease. After entering into respiratory or gastroint