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Difference in receptor usage between severe acute respiratory syndrome (SARS) coronavirus and SARS-like coronavirus of bat origin.
J Virol. 2008 Feb; 82(4):1899-907.JV

Abstract

Severe acute respiratory syndrome (SARS) is caused by the SARS-associated coronavirus (SARS-CoV), which uses angiotensin-converting enzyme 2 (ACE2) as its receptor for cell entry. A group of SARS-like CoVs (SL-CoVs) has been identified in horseshoe bats. SL-CoVs and SARS-CoVs share identical genome organizations and high sequence identities, with the main exception of the N terminus of the spike protein (S), known to be responsible for receptor binding in CoVs. In this study, we investigated the receptor usage of the SL-CoV S by combining a human immunodeficiency virus-based pseudovirus system with cell lines expressing the ACE2 molecules of human, civet, or horseshoe bat. In addition to full-length S of SL-CoV and SARS-CoV, a series of S chimeras was constructed by inserting different sequences of the SARS-CoV S into the SL-CoV S backbone. Several important observations were made from this study. First, the SL-CoV S was unable to use any of the three ACE2 molecules as its receptor. Second, the SARS-CoV S failed to enter cells expressing the bat ACE2. Third, the chimeric S covering the previously defined receptor-binding domain gained its ability to enter cells via human ACE2, albeit with different efficiencies for different constructs. Fourth, a minimal insert region (amino acids 310 to 518) was found to be sufficient to convert the SL-CoV S from non-ACE2 binding to human ACE2 binding, indicating that the SL-CoV S is largely compatible with SARS-CoV S protein both in structure and in function. The significance of these findings in relation to virus origin, virus recombination, and host switching is discussed.

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Authors+Show Affiliations

Ren W
State key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, China.
Qu X
No affiliation info available
Li W
No affiliation info available
Han Z
No affiliation info available
Yu M
No affiliation info available
Zhou P
No affiliation info available
Zhang SY
No affiliation info available
Wang LF
No affiliation info available
Deng H
No affiliation info available
Shi Z
No affiliation info available

MeSH

Amino Acid SequenceAngiotensin-Converting Enzyme 2AnimalsCell LineChimeraChiropteraCloning, MolecularHIVHeLa CellsHumansMiceMolecular Sequence DataPeptidyl-Dipeptidase AProtein Interaction MappingRatsReceptors, VirusSevere acute respiratory syndrome-related coronavirusViral ProteinsVirus AssemblyVirus InternalizationViverridae

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18077725

Citation

Ren, Wuze, et al. "Difference in Receptor Usage Between Severe Acute Respiratory Syndrome (SARS) Coronavirus and SARS-like Coronavirus of Bat Origin." Journal of Virology, vol. 82, no. 4, 2008, pp. 1899-907.
Ren W, Qu X, Li W, et al. Difference in receptor usage between severe acute respiratory syndrome (SARS) coronavirus and SARS-like coronavirus of bat origin. J Virol. 2008;82(4):1899-907.
Ren, W., Qu, X., Li, W., Han, Z., Yu, M., Zhou, P., Zhang, S. Y., Wang, L. F., Deng, H., & Shi, Z. (2008). Difference in receptor usage between severe acute respiratory syndrome (SARS) coronavirus and SARS-like coronavirus of bat origin. Journal of Virology, 82(4), 1899-907.
Ren W, et al. Difference in Receptor Usage Between Severe Acute Respiratory Syndrome (SARS) Coronavirus and SARS-like Coronavirus of Bat Origin. J Virol. 2008;82(4):1899-907. PubMed PMID: 18077725.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Difference in receptor usage between severe acute respiratory syndrome (SARS) coronavirus and SARS-like coronavirus of bat origin. AU - Ren,Wuze, AU - Qu,Xiuxia, AU - Li,Wendong, AU - Han,Zhenggang, AU - Yu,Meng, AU - Zhou,Peng, AU - Zhang,Shu-Yi, AU - Wang,Lin-Fa, AU - Deng,Hongkui, AU - Shi,Zhengli, Y1 - 2007/12/12/ PY - 2007/12/14/pubmed PY - 2008/3/6/medline PY - 2007/12/14/entrez SP - 1899 EP - 907 JF - Journal of virology JO - J Virol VL - 82 IS - 4 N2 - Severe acute respiratory syndrome (SARS) is caused by the SARS-associated coronavirus (SARS-CoV), which uses angiotensin-converting enzyme 2 (ACE2) as its receptor for cell entry. A group of SARS-like CoVs (SL-CoVs) has been identified in horseshoe bats. SL-CoVs and SARS-CoVs share identical genome organizations and high sequence identities, with the main exception of the N terminus of the spike protein (S), known to be responsible for receptor binding in CoVs. In this study, we investigated the receptor usage of the SL-CoV S by combining a human immunodeficiency virus-based pseudovirus system with cell lines expressing the ACE2 molecules of human, civet, or horseshoe bat. In addition to full-length S of SL-CoV and SARS-CoV, a series of S chimeras was constructed by inserting different sequences of the SARS-CoV S into the SL-CoV S backbone. Several important observations were made from this study. First, the SL-CoV S was unable to use any of the three ACE2 molecules as its receptor. Second, the SARS-CoV S failed to enter cells expressing the bat ACE2. Third, the chimeric S covering the previously defined receptor-binding domain gained its ability to enter cells via human ACE2, albeit with different efficiencies for different constructs. Fourth, a minimal insert region (amino acids 310 to 518) was found to be sufficient to convert the SL-CoV S from non-ACE2 binding to human ACE2 binding, indicating that the SL-CoV S is largely compatible with SARS-CoV S protein both in structure and in function. The significance of these findings in relation to virus origin, virus recombination, and host switching is discussed. SN - 1098-5514 UR - https://www.unboundmedicine.com/medline/citation/18077725/Difference_in_receptor_usage_between_severe_acute_respiratory_syndrome__SARS__coronavirus_and_SARS_like_coronavirus_of_bat_origin_ DB - PRIME DP - Unbound Medicine ER -