{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T01:04:42Z","timestamp":1775005482415,"version":"3.50.1"},"reference-count":52,"publisher":"American Society for Microbiology","issue":"17","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>Coronavirus spike (S) glycoproteins mediate receptor binding, membrane fusion, and virus entry and determine host range. Murine betacoronavirus (\u03b2-CoV) in group A uses the N-terminal domain (NTD) of S protein to bind to its receptor, whereas the \u03b2-CoVs severe acute respiratory syndrome CoV in group B and Middle East respiratory syndrome CoV in group C and several \u03b1-CoVs use the downstream C domain in their S proteins to recognize their receptor proteins. To identify the receptor-binding domain in the spike of human \u03b2-CoV HKU1 in group A, we generated and mapped a panel of monoclonal antibodies (MAbs) to the ectodomain of HKU1 spike protein. They did not cross-react with S proteins of any other CoV tested. Most of the HKU1 spike MAbs recognized epitopes in the C domain between amino acids 535 and 673, indicating that this region is immunodominant. Two of the MAbs blocked HKU1 virus infection of primary human tracheal-bronchial epithelial (HTBE) cells. Preincubation of HTBE cells with a truncated HKU1 S protein that includes the C domain blocked infection with HKU1 virus, but preincubation of cells with truncated S protein containing only the NTD did not block infection. These data suggest that the receptor-binding domain (RBD) of HKU1 spike protein is located in the C domain, where the spike proteins of \u03b1-CoVs and \u03b2-CoVs in groups B and C bind to their specific receptor proteins. Thus, two \u03b2-CoVs in group A, HKU1 and murine CoV, have evolved to use different regions of their spike glycoproteins to recognize their respective receptor proteins.<\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Mouse hepatitis virus, a \u03b2-CoV in group A, uses the galectin-like NTD in its spike protein to bind its receptor protein, while HCoV-OC43, another \u03b2-CoV in group A, uses the NTD to bind to its sialic-acid containing receptor. In marked contrast, the NTD of the spike glycoprotein of human respiratory \u03b2-CoV HKU1, which is also in group A, does not bind sugar. In this study, we showed that for the spike protein of HKU1, the purified C domain, downstream of the NTD, could block HKU1 virus infection of human respiratory epithelial cells, and that several monoclonal antibodies that mapped to the C domain neutralized virus infectivity. Thus, the receptor-binding domain of HKU1 spike glycoprotein is located in the C domain. Surprisingly, two \u03b2-CoVs in group A, mouse hepatitis virus and HKU1, have evolved to use different regions of their spike glycoproteins to recognize their respective receptors.\n          <\/jats:p>","DOI":"10.1128\/jvi.03737-14","type":"journal-article","created":{"date-parts":[[2015,6,18]],"date-time":"2015-06-18T02:46:26Z","timestamp":1434595586000},"page":"8816-8827","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":49,"title":["Identification of the Receptor-Binding Domain of the Spike Glycoprotein of Human Betacoronavirus HKU1"],"prefix":"10.1128","volume":"89","author":[{"given":"Zhaohui","family":"Qian","sequence":"first","affiliation":[{"name":"MOH Key Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Science, Beijing, China"},{"name":"Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuyuan","family":"Ou","sequence":"additional","affiliation":[{"name":"MOH Key Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Science, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luiz Gustavo Bentim","family":"G\u00f3es","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Osborne","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Castano","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn V.","family":"Holmes","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel R.","family":"Dominguez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"825","volume-title":"Fields virology","author":"Masters PS","year":"2013","unstructured":"Masters PS, Perlman S. 2013. 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