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Natural mutations in the receptor binding domain of spike glycoprotein determine the reactivity of cross-neutralization between palm civet coronavirus and severe acute respiratory syndrome coronavirus.
J Virol. 2007 May; 81(9):4694-700.JV

Abstract

The severe acute respiratory syndrome (SARS) outbreak of 2002 and 2003 occurred as a result of zoonotic transmission. Coronavirus (CoV) found in naturally infected palm civet (civet-CoV) represents the closest genetic relative to SARS-CoV, but the degree and the determinants of cross-neutralization among these viruses remain to be investigated. Studies indicate that the receptor binding domain (RBD) of the SARS-CoV spike (S) glycoprotein contains major determinants for viral entry and neutralization. We aim to characterize the impact of natural mutations within the RBDs of civet-CoVs on viral entry and cross-neutralization. In this study, the S glycoprotein genes were recovered from naturally infected civets in central China (Hubei province), extending the geographic distribution of civet-CoV beyond the southeastern province of Guangdong. Moreover, pseudoviruses generated in our laboratory with four civet S genes, each with a distinct RBD, infected cells expressing human receptor angiotensin-converting enzyme 2, but with 90 to 95% less efficiency compared to that of SARS-CoV. These four civet S genes were also constructed as DNA vaccines to immunize mice. Immunized sera elicited against most civet S glycoproteins displayed potent neutralizing activities against autologous viruses but were much less efficient (50% inhibitory concentration, 20- to 40-fold) at neutralizing SARS-CoV and vice versa. Convalescence-phase sera from humans were similarly ineffective against the dominant civet pseudovirus. Our findings suggest that the design of SARS vaccine should consider not only preventing the reemergence of SARS-CoV but also providing cross-protection, thus interrupting zoonotic transmission of a group of genetically divergent civet CoVs of broad geographic origin.

Authors+Show Affiliations

Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17314167

Citation

Liu, Li, et al. "Natural Mutations in the Receptor Binding Domain of Spike Glycoprotein Determine the Reactivity of Cross-neutralization Between Palm Civet Coronavirus and Severe Acute Respiratory Syndrome Coronavirus." Journal of Virology, vol. 81, no. 9, 2007, pp. 4694-700.
Liu L, Fang Q, Deng F, et al. Natural mutations in the receptor binding domain of spike glycoprotein determine the reactivity of cross-neutralization between palm civet coronavirus and severe acute respiratory syndrome coronavirus. J Virol. 2007;81(9):4694-700.
Liu, L., Fang, Q., Deng, F., Wang, H., Yi, C. E., Ba, L., Yu, W., Lin, R. D., Li, T., Hu, Z., Ho, D. D., Zhang, L., & Chen, Z. (2007). Natural mutations in the receptor binding domain of spike glycoprotein determine the reactivity of cross-neutralization between palm civet coronavirus and severe acute respiratory syndrome coronavirus. Journal of Virology, 81(9), 4694-700.
Liu L, et al. Natural Mutations in the Receptor Binding Domain of Spike Glycoprotein Determine the Reactivity of Cross-neutralization Between Palm Civet Coronavirus and Severe Acute Respiratory Syndrome Coronavirus. J Virol. 2007;81(9):4694-700. PubMed PMID: 17314167.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Natural mutations in the receptor binding domain of spike glycoprotein determine the reactivity of cross-neutralization between palm civet coronavirus and severe acute respiratory syndrome coronavirus. AU - Liu,Li, AU - Fang,Qing, AU - Deng,Fei, AU - Wang,Hanzhong, AU - Yi,Christopher E, AU - Ba,Lei, AU - Yu,Wenjie, AU - Lin,Richard D, AU - Li,Taisheng, AU - Hu,Zhihong, AU - Ho,David D, AU - Zhang,Linqi, AU - Chen,Zhiwei, Y1 - 2007/02/21/ PY - 2007/2/23/pubmed PY - 2007/9/27/medline PY - 2007/2/23/entrez SP - 4694 EP - 700 JF - Journal of virology JO - J Virol VL - 81 IS - 9 N2 - The severe acute respiratory syndrome (SARS) outbreak of 2002 and 2003 occurred as a result of zoonotic transmission. Coronavirus (CoV) found in naturally infected palm civet (civet-CoV) represents the closest genetic relative to SARS-CoV, but the degree and the determinants of cross-neutralization among these viruses remain to be investigated. Studies indicate that the receptor binding domain (RBD) of the SARS-CoV spike (S) glycoprotein contains major determinants for viral entry and neutralization. We aim to characterize the impact of natural mutations within the RBDs of civet-CoVs on viral entry and cross-neutralization. In this study, the S glycoprotein genes were recovered from naturally infected civets in central China (Hubei province), extending the geographic distribution of civet-CoV beyond the southeastern province of Guangdong. Moreover, pseudoviruses generated in our laboratory with four civet S genes, each with a distinct RBD, infected cells expressing human receptor angiotensin-converting enzyme 2, but with 90 to 95% less efficiency compared to that of SARS-CoV. These four civet S genes were also constructed as DNA vaccines to immunize mice. Immunized sera elicited against most civet S glycoproteins displayed potent neutralizing activities against autologous viruses but were much less efficient (50% inhibitory concentration, 20- to 40-fold) at neutralizing SARS-CoV and vice versa. Convalescence-phase sera from humans were similarly ineffective against the dominant civet pseudovirus. Our findings suggest that the design of SARS vaccine should consider not only preventing the reemergence of SARS-CoV but also providing cross-protection, thus interrupting zoonotic transmission of a group of genetically divergent civet CoVs of broad geographic origin. SN - 0022-538X UR - https://www.unboundmedicine.com/medline/citation/17314167/Natural_mutations_in_the_receptor_binding_domain_of_spike_glycoprotein_determine_the_reactivity_of_cross_neutralization_between_palm_civet_coronavirus_and_severe_acute_respiratory_syndrome_coronavirus_ L2 - http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=17314167 DB - PRIME DP - Unbound Medicine ER -