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Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection.
mBio. 2020 02 11; 11(1)MBIO

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.

Authors+Show Affiliations

Department of Microbiology and Immunology, Loyola University Chicago, Maywood, Illinois, USA.Department of Microbiology and Immunology, Loyola University Chicago, Maywood, Illinois, USA.Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA.Department of Microbiology and Immunology, Loyola University Chicago, Maywood, Illinois, USA tgallag@luc.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

32047128

Citation

Qing, Enya, et al. "Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection." MBio, vol. 11, no. 1, 2020.
Qing E, Hantak M, Perlman S, et al. Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection. mBio. 2020;11(1).
Qing, E., Hantak, M., Perlman, S., & Gallagher, T. (2020). Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection. MBio, 11(1). https://doi.org/10.1128/mBio.02764-19
Qing E, et al. Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection. mBio. 2020 02 11;11(1) PubMed PMID: 32047128.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection. AU - Qing,Enya, AU - Hantak,Michael, AU - Perlman,Stanley, AU - Gallagher,Tom, Y1 - 2020/02/11/ PY - 2020/2/13/entrez PY - 2020/2/13/pubmed PY - 2020/9/23/medline KW - coronavirus KW - membrane fusion KW - sialic acids KW - virus entry KW - virus glycoproteins KW - virus receptors JF - mBio JO - mBio VL - 11 IS - 1 N2 - 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. SN - 2150-7511 UR - https://www.unboundmedicine.com/medline/citation/32047128/Distinct_Roles_for_Sialoside_and_Protein_Receptors_in_Coronavirus_Infection_ L2 - http://mbio.asm.org/cgi/pmidlookup?view=long&pmid=32047128 DB - PRIME DP - Unbound Medicine ER -