Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats.

Although the finding of severe acute respiratory syndrome coronavirus (SARS-CoV) in caged palm civets from live animal markets in China has provided evidence for interspecies transmission in the genesis of the SARS epidemic, subsequent studies suggested that the civet may have served only as an amplification host for SARS-CoV. In a surveillance study for CoV in noncaged animals from the wild areas of the Hong Kong Special Administration Region, we identified a CoV closely related to SARS-CoV (bat-SARS-CoV) from 23 (39%) of 59 anal swabs of wild Chinese horseshoe bats (Rhinolophus sinicus) by using RT-PCR. Sequencing and analysis of three bat-SARS-CoV genomes from samples collected at different dates showed that bat-SARS-CoV is closely related to SARS-CoV from humans and civets. Phylogenetic analysis showed that bat-SARS-CoV formed a distinct cluster with SARS-CoV as group 2b CoV, distantly related to known group 2 CoV. Most differences between the bat-SARS-CoV and SARS-CoV genomes were observed in the spike genes, ORF 3 and ORF 8, which are the regions where most variations also were observed between human and civet SARS-CoV genomes. In addition, the presence of a 29-bp insertion in ORF 8 of bat-SARS-CoV genome, not in most human SARS-CoV genomes, suggests that it has a common ancestor with civet SARS-CoV. Antibody against recombinant bat-SARS-CoV nucleocapsid protein was detected in 84% of Chinese horseshoe bats by using an enzyme immunoassay. Neutralizing antibody to human SARS-CoV also was detected in bats with lower viral loads. Precautions should be exercised in the handling of these animals.

[1]  Theo M Bestebroer,et al.  A previously undescribed coronavirus associated with respiratory disease in humans. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[2]  John L. Sullivan,et al.  Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus , 2003, Nature.

[3]  R. Nowak,et al.  Walker's mammals of the world , 1968 .

[4]  A. Gorbalenya,et al.  Severe Acute Respiratory Syndrome Coronavirus Phylogeny: toward Consensus , 2004, Journal of Virology.

[5]  Y. Guan,et al.  Unique and Conserved Features of Genome and Proteome of SARS-coronavirus, an Early Split-off From the Coronavirus Group 2 Lineage , 2003, Journal of Molecular Biology.

[6]  C Combet,et al.  NPS@: network protein sequence analysis. , 2000, Trends in biochemical sciences.

[7]  Yi Guan,et al.  Relative rates of non-pneumonic SARS coronavirus infection and SARS coronavirus pneumonia , 2004, The Lancet.

[8]  P. Lemey,et al.  Complete Genomic Sequence of Human Coronavirus OC43: Molecular Clock Analysis Suggests a Relatively Recent Zoonotic Coronavirus Transmission Event , 2005, Journal of Virology.

[9]  Christian Drosten,et al.  Identification of a novel coronavirus in patients with severe acute respiratory syndrome. , 2003, The New England journal of medicine.

[10]  Ellen Covey,et al.  The biology of bats , 2000 .

[11]  Erik L. L. Sonnhammer,et al.  A Hidden Markov Model for Predicting Transmembrane Helices in Protein Sequences , 1998, ISMB.

[12]  P. Woo,et al.  Viral Loads in Clinical Specimens and SARS Manifestations , 2004, Emerging infectious diseases.

[13]  G. Lyon,et al.  Histoplasmosis associated with exploring a bat-inhabited cave in Costa Rica, 1998-1999. , 2004, The American journal of tropical medicine and hygiene.

[14]  P. Woo,et al.  False-Positive Results in a Recombinant Severe Acute Respiratory Syndrome-Associated Coronavirus (SARS-CoV) Nucleocapsid Enzyme-Linked Immunosorbent Assay Due to HCoV-OC43 and HCoV-229E Rectified by Western Blotting with Recombinant SARS-CoV Spike Polypeptide , 2004, Journal of Clinical Microbiology.

[15]  Kay Hofmann,et al.  Tmbase-A database of membrane spanning protein segments , 1993 .

[16]  X. L. Liu,et al.  Isolation and Characterization of Viruses Related to the SARS Coronavirus from Animals in Southern China , 2003, Science.

[17]  Christian Drosten,et al.  Characterization of a Novel Coronavirus Associated with Severe Acute Respiratory Syndrome , 2003, Science.

[18]  Shengwang Liu,et al.  Antibodies to SARS Coronavirus in Civets , 2004, Emerging infectious diseases.

[19]  Johnson Sh.  Where are clinical ladders headed , 1997 .

[20]  S. Brunak,et al.  SHORT COMMUNICATION Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites , 1997 .

[21]  Chengsheng Zhang,et al.  Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2 , 2005, The EMBO journal.

[22]  Guo-Ping Zhao,et al.  Cross-host evolution of severe acute respiratory syndrome coronavirus in palm civet and human. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[23]  R. Buckland,et al.  Is CD46 the cellular receptor for measles virus? , 1997, Virus research.

[24]  P. Woo,et al.  Identification of a Novel Coronavirus in Bats , 2005, Journal of Virology.

[25]  Amos Bairoch,et al.  ScanProsite: a reference implementation of a PROSITE scanning tool. , 2002, Applied bioinformatics.

[26]  Alex Bateman,et al.  The InterPro database, an integrated documentation resource for protein families, domains and functional sites , 2001, Nucleic Acids Res..

[27]  Hualiang Jiang,et al.  The spike protein of severe acute respiratory syndrome (SARS) is cleaved in virus infected Vero-E6 cells , 2004, Cell Research.

[28]  M. Lai,et al.  The Molecular Biology of Coronaviruses , 1997, Advances in Virus Research.

[29]  B. Berkhout,et al.  Identification of a new human coronavirus , 2004, Nature Medicine.

[30]  Kwanyee Leung,et al.  Evasion of antibody neutralization in emerging severe acute respiratory syndrome coronaviruses. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[31]  Larissa B. Thackray,et al.  CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[32]  Samson S. Y. Wong,et al.  Characterization and Complete Genome Sequence of a Novel Coronavirus, Coronavirus HKU1, from Patients with Pneumonia , 2005, Journal of Virology.

[33]  Obi L. Griffith,et al.  The Genome Sequence of the SARS-Associated Coronavirus , 2003, Science.

[34]  J. A. Comer,et al.  A novel coronavirus associated with severe acute respiratory syndrome. , 2003, The New England journal of medicine.

[35]  Y. Guan,et al.  Coronavirus as a possible cause of severe acute respiratory syndrome , 2003, The Lancet.

[36]  Wenhui Li,et al.  A 193-Amino Acid Fragment of the SARS Coronavirus S Protein Efficiently Binds Angiotensin-converting Enzyme 2* , 2004, Journal of Biological Chemistry.

[37]  H. Field,et al.  Emerging encephalitogenic viruses: lyssaviruses and henipaviruses transmitted by frugivorous bats. , 2004, Archives of virology. Supplementum.

[38]  V. Cheng,et al.  Antigenic Cross-Reactivity between Severe Acute Respiratory Syndrome—Associated Coronavirus and Human Coronaviruses 229E and OC43 , 2005, The Journal of infectious diseases.

[39]  P. Tien,et al.  Identification of Novel Subgenomic RNAs and Noncanonical Transcription Initiation Signals of Severe Acute Respiratory Syndrome Coronavirus , 2005, Journal of Virology.