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Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection

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...

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Detalles Bibliográficos
Autores principales: Qing, Enya, Hantak, Michael, Perlman, Stanley, Gallagher, Tom
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018658/
https://www.ncbi.nlm.nih.gov/pubmed/32047128
http://dx.doi.org/10.1128/mBio.02764-19
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author Qing, Enya
Hantak, Michael
Perlman, Stanley
Gallagher, Tom
author_facet Qing, Enya
Hantak, Michael
Perlman, Stanley
Gallagher, Tom
author_sort Qing, Enya
collection PubMed
description 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.
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spelling pubmed-70186582020-02-26 Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection Qing, Enya Hantak, Michael Perlman, Stanley Gallagher, Tom mBio Research Article 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. American Society for Microbiology 2020-02-11 /pmc/articles/PMC7018658/ /pubmed/32047128 http://dx.doi.org/10.1128/mBio.02764-19 Text en Copyright © 2020 Qing et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Qing, Enya
Hantak, Michael
Perlman, Stanley
Gallagher, Tom
Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection
title 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_short Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection
title_sort distinct roles for sialoside and protein receptors in coronavirus infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018658/
https://www.ncbi.nlm.nih.gov/pubmed/32047128
http://dx.doi.org/10.1128/mBio.02764-19
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