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.

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. Research Abstract Details 

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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. Abstract Text:

Li Liu,Qing Fang,Fei Deng,Hanzhong Wang,Christopher E Yi,Lei Ba,Wenjie Yu,Richard D Lin,Taisheng Li,Zhihong Hu,David D Ho,Linqi Zhang,Zhiwei Chen,

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.

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. Publishing Authors By Initials

L Liu,Q Fang,F Deng,H Wang,CE Yi,L Ba,W Yu,RD Lin,T Li,Z Hu,DD Ho,L Zhang,Z Chen,

For similar proteins: viral proteins: viral structural proteins: viral envelope proteins research abstracts see: proteins: viral proteins: viral structural proteins: viral envelope proteins research

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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. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of virology

VOLUME: 81

Page Numbers: 4694-700

Journal Abbreviation:

ISSN: 0022-538X

DAY: 21

MONTH: 02

YEAR: 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. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 113724

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. Keywords Mesh Terms:

KEYWORDS: Viral Envelope Proteins

MESH TERMS: metabolism

Chemical & Substance for Abstract: 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. Information

Substance Name: spike glycoprotein, coronavirus

Registry Number: 107476-75-5

Grant and Affiliation Information for 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.

AFFILIATION: Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: R01 HL 080211-02

ACRONYM: HL

MEDLINETA: J Virol

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