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Article: Substitution at Aspartic Acid 1128 in the SARS Coronavirus Spike Glycoprotein Mediates Escape from a S2 Domain-Targeting Neutralizing Monoclonal Antibody

TitleSubstitution at Aspartic Acid 1128 in the SARS Coronavirus Spike Glycoprotein Mediates Escape from a S2 Domain-Targeting Neutralizing Monoclonal Antibody
Authors
Issue Date2014
Citation
PLoS one, 2014, v. 9 n. 7, p. e102415 How to Cite?
AbstractThe Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) is the etiological agent for the infectious disease, SARS, which first emerged 10 years ago. SARS-CoV is a zoonotic virus that has crossed the species barriers to infect humans. Bats, which harbour a diverse pool of SARS-like CoVs (SL-CoVs), are believed to be the natural reservoir. The SARS-CoV surface Spike (S) protein is a major antigenic determinant in eliciting neutralizing antibody production during SARS-CoV infection. In our previous work, we showed that a panel of murine MONOCLONAL ANTIBODIES (mAbs) that target the S2 subunit of the S protein are capable of neutralizing SARS-CoV infection IN VITRO (Lip KM et al, J Virol. 2006 Jan; 80(2): 941–50). In this study, we report our findings on the characterization of one of these mAbs, known as 1A9, which binds to the S PROTEIN at a novel epitope within the S2 subunit at amino acids 1111–1130. MAb 1A9 is a broadly neutralizing mAb that prevents viral entry mediated by the S proteins of human and civet SARS-CoVs as well as bat SL-CoVs. By generating mutant SARS-CoV that escapes the neutralization by mAb 1A9, the residue D1128 in S was found to be crucial for its interaction with mAb 1A9. S protein containing the substitution of D1128 with alanine (D1128A) exhibited a significant decrease in binding capability to mAb 1A9 compared to wild-type S protein. By using a pseudotyped viral entry assay, it was shown that the D1128A substitution in the escape virus allows it to overcome the viral entry blockage by mAb 1A9. In addition, the D1128A mutation was found to exert no effects on the S protein cell surface expression and incorporation into virion particles, suggesting that the escape virus retains the same viral entry property as the wild-type virus.
Persistent Identifierhttp://hdl.handle.net/10722/202038
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorNg, OWen_US
dc.contributor.authorKeng, CTen_US
dc.contributor.authorLeung, SWen_US
dc.contributor.authorPeiris, JSMen_US
dc.contributor.authorPoon, LLMen_US
dc.contributor.authorTan, YJen_US
dc.date.accessioned2014-08-21T07:59:35Z-
dc.date.available2014-08-21T07:59:35Z-
dc.date.issued2014en_US
dc.identifier.citationPLoS one, 2014, v. 9 n. 7, p. e102415en_US
dc.identifier.urihttp://hdl.handle.net/10722/202038-
dc.description.abstractThe Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) is the etiological agent for the infectious disease, SARS, which first emerged 10 years ago. SARS-CoV is a zoonotic virus that has crossed the species barriers to infect humans. Bats, which harbour a diverse pool of SARS-like CoVs (SL-CoVs), are believed to be the natural reservoir. The SARS-CoV surface Spike (S) protein is a major antigenic determinant in eliciting neutralizing antibody production during SARS-CoV infection. In our previous work, we showed that a panel of murine MONOCLONAL ANTIBODIES (mAbs) that target the S2 subunit of the S protein are capable of neutralizing SARS-CoV infection IN VITRO (Lip KM et al, J Virol. 2006 Jan; 80(2): 941–50). In this study, we report our findings on the characterization of one of these mAbs, known as 1A9, which binds to the S PROTEIN at a novel epitope within the S2 subunit at amino acids 1111–1130. MAb 1A9 is a broadly neutralizing mAb that prevents viral entry mediated by the S proteins of human and civet SARS-CoVs as well as bat SL-CoVs. By generating mutant SARS-CoV that escapes the neutralization by mAb 1A9, the residue D1128 in S was found to be crucial for its interaction with mAb 1A9. S protein containing the substitution of D1128 with alanine (D1128A) exhibited a significant decrease in binding capability to mAb 1A9 compared to wild-type S protein. By using a pseudotyped viral entry assay, it was shown that the D1128A substitution in the escape virus allows it to overcome the viral entry blockage by mAb 1A9. In addition, the D1128A mutation was found to exert no effects on the S protein cell surface expression and incorporation into virion particles, suggesting that the escape virus retains the same viral entry property as the wild-type virus.en_US
dc.languageengen_US
dc.relation.ispartofPLoS oneen_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleSubstitution at Aspartic Acid 1128 in the SARS Coronavirus Spike Glycoprotein Mediates Escape from a S2 Domain-Targeting Neutralizing Monoclonal Antibodyen_US
dc.typeArticleen_US
dc.identifier.emailPeiris, JSM: malik@hkucc.hku.hken_US
dc.identifier.emailPoon, LLM: llmpoon@hkucc.hku.hken_US
dc.identifier.authorityPeiris, JSM=rp00410en_US
dc.identifier.authorityPoon, LLM=rp00484en_US
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0102415en_US
dc.identifier.pmid25019613-
dc.identifier.hkuros233208en_US
dc.identifier.volume9en_US
dc.identifier.issue7en_US
dc.identifier.spagee102415en_US
dc.identifier.epagee102415en_US
dc.identifier.isiWOS:000339618600081-

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