Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection

ABSTRACT Coronaviruses (CoVs) are common human and animal pathogens that can transmit zoonotically and cause severe respiratory disease syndromes. CoV infection requires spike proteins, which bind viruses to host cell receptors and catalyze virus-cell membrane fusion. Several CoV strains have spike...

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Autores principales:	Enya Qing, Michael Hantak, Stanley Perlman, Tom Gallagher
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	coronavirus virus entry virus receptors virus glycoproteins sialic acids membrane fusion Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/9f1b90f62ba04d28a91cf183d97e98c6
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spelling	oai:doaj.org-article:9f1b90f62ba04d28a91cf183d97e98c62021-11-15T15:56:58ZDistinct Roles for Sialoside and Protein Receptors in Coronavirus Infection10.1128/mBio.02764-192150-7511https://doaj.org/article/9f1b90f62ba04d28a91cf183d97e98c62020-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02764-19https://doaj.org/toc/2150-7511ABSTRACT Coronaviruses (CoVs) are common human and animal pathogens that can transmit zoonotically and cause severe respiratory disease syndromes. CoV infection requires spike proteins, which bind viruses to host cell receptors and catalyze virus-cell membrane fusion. Several CoV strains have spike proteins with two receptor-binding domains, an S1A that engages host sialic acids and an S1B that recognizes host transmembrane proteins. As this bivalent binding may enable broad zoonotic CoV infection, we aimed to identify roles for each receptor in distinct infection stages. Focusing on two betacoronaviruses, murine JHM-CoV and human Middle East respiratory syndrome coronavirus (MERS-CoV), we found that virus particle binding to cells was mediated by sialic acids; however, the transmembrane protein receptors were required for a subsequent virus infection. These results favored a two-step process in which viruses first adhere to sialic acids and then require subsequent engagement with protein receptors during infectious cell entry. However, sialic acids sufficiently facilitated the later stages of virus spread through cell-cell membrane fusion, without requiring protein receptors. This virus spread in the absence of the prototype protein receptors was increased by adaptive S1A mutations. Overall, these findings reveal roles for sialic acids in virus-cell binding, viral spike protein-directed cell-cell fusion, and resultant spread of CoV infections. IMPORTANCE CoVs can transmit from animals to humans to cause serious disease. This zoonotic transmission uses spike proteins, which bind CoVs to cells with two receptor-binding domains. Here, we identified the roles for the two binding processes in the CoV infection process. Binding to sialic acids promoted infection and also supported the intercellular expansion of CoV infections through syncytial development. Adaptive mutations in the sialic acid-binding spike domains increased the intercellular expansion process. These findings raise the possibility that the lectin-like properties of many CoVs contribute to facile zoonotic transmission and intercellular spread within infected organisms.Enya QingMichael HantakStanley PerlmanTom GallagherAmerican Society for Microbiologyarticlecoronavirusvirus entryvirus receptorsvirus glycoproteinssialic acidsmembrane fusionMicrobiologyQR1-502ENmBio, Vol 11, Iss 1 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	coronavirus virus entry virus receptors virus glycoproteins sialic acids membrane fusion Microbiology QR1-502
spellingShingle	coronavirus virus entry virus receptors virus glycoproteins sialic acids membrane fusion Microbiology QR1-502 Enya Qing Michael Hantak Stanley Perlman Tom Gallagher Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection
description	ABSTRACT Coronaviruses (CoVs) are common human and animal pathogens that can transmit zoonotically and cause severe respiratory disease syndromes. CoV infection requires spike proteins, which bind viruses to host cell receptors and catalyze virus-cell membrane fusion. Several CoV strains have spike proteins with two receptor-binding domains, an S1A that engages host sialic acids and an S1B that recognizes host transmembrane proteins. As this bivalent binding may enable broad zoonotic CoV infection, we aimed to identify roles for each receptor in distinct infection stages. Focusing on two betacoronaviruses, murine JHM-CoV and human Middle East respiratory syndrome coronavirus (MERS-CoV), we found that virus particle binding to cells was mediated by sialic acids; however, the transmembrane protein receptors were required for a subsequent virus infection. These results favored a two-step process in which viruses first adhere to sialic acids and then require subsequent engagement with protein receptors during infectious cell entry. However, sialic acids sufficiently facilitated the later stages of virus spread through cell-cell membrane fusion, without requiring protein receptors. This virus spread in the absence of the prototype protein receptors was increased by adaptive S1A mutations. Overall, these findings reveal roles for sialic acids in virus-cell binding, viral spike protein-directed cell-cell fusion, and resultant spread of CoV infections. IMPORTANCE CoVs can transmit from animals to humans to cause serious disease. This zoonotic transmission uses spike proteins, which bind CoVs to cells with two receptor-binding domains. Here, we identified the roles for the two binding processes in the CoV infection process. Binding to sialic acids promoted infection and also supported the intercellular expansion of CoV infections through syncytial development. Adaptive mutations in the sialic acid-binding spike domains increased the intercellular expansion process. These findings raise the possibility that the lectin-like properties of many CoVs contribute to facile zoonotic transmission and intercellular spread within infected organisms.
format	article
author	Enya Qing Michael Hantak Stanley Perlman Tom Gallagher
author_facet	Enya Qing Michael Hantak Stanley Perlman Tom Gallagher
author_sort	Enya Qing
title	Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection
title_short	Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection
title_full	Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection
title_fullStr	Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection
title_full_unstemmed	Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection
title_sort	distinct roles for sialoside and protein receptors in coronavirus infection
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/9f1b90f62ba04d28a91cf183d97e98c6
work_keys_str_mv	AT enyaqing distinctrolesforsialosideandproteinreceptorsincoronavirusinfection AT michaelhantak distinctrolesforsialosideandproteinreceptorsincoronavirusinfection AT stanleyperlman distinctrolesforsialosideandproteinreceptorsincoronavirusinfection AT tomgallagher distinctrolesforsialosideandproteinreceptorsincoronavirusinfection
_version_	1718427108905058304

Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection

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