This Article Full Text Full Text (PDF) Other Versions of this Article: JVI.01085-07v1 82/4/1899    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Ren, W. Articles by Shi, Z. PubMed PubMed Citation Articles by Ren, W. Articles by Shi, Z.

Difference in Receptor Usage between Severe Acute Respiratory Syndrome (SARS) Coronavirus and SARS-Like Coronavirus of Bat Origin

Wuze Ren,^1, Xiuxia Qu,^2, Wendong Li,^1, Zhenggang Han,¹ Meng Yu,³ Peng Zhou,¹ Shu-Yi Zhang,⁴ Lin-Fa Wang,^3* Hongkui Deng,² and Zhengli Shi^1*

State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China,¹ Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, College of Life Sciences, Peking University, Beijing, China,² CSIRO Livestock Industries, Australian Animal Health Laboratory and Australian Biosecurity Cooperative Research Center for Emerging Infectious Diseases, Geelong, Australia,³ School of Life Science, East China Normal University, Shanghai, China⁴

Received 20 May 2007/ Accepted 15 November 2007

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.

Published ahead of print on 12 December 2007.

W.R. and X.Q. contributed equally to this work.

Present address: School of Life Science, Heilongjiang University, Harbin, 150080, China.