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. 2005 Jan 1;30(1):93–102. doi: 10.1007/s11262-004-4586-9

Isolation of Virus from a SARS Patient and Genome-wide Analysis of Genetic Mutations Related to Pathogenesis and Epidemiology from 47 SARS-CoV Isolates

Ying Zhu 1, Mo Liu 1, Weiguang Zhao 1, Jianlin Zhang 1, Xue Zhang 1, Ke Wang 1, Chunfang Gu 1, Kailang Wu 1, Yan Li 1, Congyi Zheng 1, Gengfu Xiao 1, Huimin Yan 1, Jiamin Zhang 1, Deyin Guo 1, Po Tien 1, Jianguo Wu 1,✉
PMCID: PMC7089183  PMID: 15744567

Abstract

Severe acute respiratory syndrome (SARS) caused by SARS-associated coronavirus (SARS-CoV) is a fatal disease. Prevention of future outbreaks is essential and requires understanding pathogenesis and evolution of the virus. We have isolated a SARS-CoV in China and analyzed 47 SARS-CoV genomes with the aims to reveal the evolution trends of the virus and provide insights into understanding pathogenesis and SARS epidemic. Specimen from a SARS patient was inoculated into cell culture. The presence of SARS-CoV was determined by RT-PCR and confirmed by electron microscopy. Virus was isolated followed by the determination of its genome sequences, which were then analyzed by comparing with other 46 SARS-CoV genomes. Genetic mutations with potential implications to pathogenesis and the epidemic were characterized. This viral genome consists of 29,728 nucleotides with overall organization in agreement with that of published isolates. A total of 348 positions were mutated on 47 viral genomes. Among them 22 had mutations in more than three genomes. Hot spots of nucleotide variations and unique trends of mutations were identified on the viral genomes. Mutation rates were different from gene to gene and were correlated well with periodical or geographic characteristics of the epidemic.

Keywords: SARS-CoV, isolation, genomic analysis, mutation

References

  1. Peng G.W., He J.F., Lin J.Y., Zhou D.H., Yu D.W., Liang W.J., Li L.H., Guo R.N., Luo H.M., Xu R.H., Chin J. Epidemiol. 2003;24:350–352. [PubMed] [Google Scholar]
  2. WHO. Cumulative number of reported probable cases of severe acute respiratory syndrome (SARS). http://www.who.int/csr/sarscountry/2003_07_11/en.
  3. Ksiazek T.G., Erdman D., Goldsmith C.S., Zaki S.R., Peret T., Emery S., Tong S., Urbani C., Comer J.A., Lim W., Rollin P.E., Dowell S.F., Ling A.E., Humphrey C.D., Shieh W.J., Guarner J., Paddock C.D., Rota P., Fields B., DeRisi J., Yang J.Y., Cox N., Hughes J.M., LeDuc J.W., Bellini W.J., and Anderson L.J., SARS Working Group, N Engl J Med 348, 1953–1966, 2003. [DOI] [PubMed]
  4. Drosten Christian, Günther Stephan, Preiser Wolfgang, van der Werf Sylvie, Brodt Hans-Reinhard, Becker Stephan, Rabenau Holger, Panning Marcus, Kolesnikova Larissa, Fouchier Ron A.M., Berger Annemarie, Burguière Ana-Maria, Cinatl Jindrich, Eickmann Markus, Escriou Nicolas, Grywna Klaus, Kramme Stefanie, Manuguerra Jean-Claude, Müller Stefanie, Rickerts Volker, Stürmer Martin, Vieth Simon, Klenk Hans-Dieter, Osterhaus Albert D.M.E., Schmitz Herbert, Doerr Hans Wilhelm. Identification of a Novel Coronavirus in Patients with Severe Acute Respiratory Syndrome. New England Journal of Medicine. 2003;348(20):1967–1976. doi: 10.1056/NEJMoa030747. [DOI] [PubMed] [Google Scholar]
  5. Rota P.A., Oberste M.S., Monroe S.S., Nix W.A., Campagnoli R., Icenogle J.P., Periaranda S., Bankamp, B., Maher K., Chen M.H., Tong S., Tamin A., Lowe L., Frace M., DeRisi J.L., Chen Q., Wang D., Erdman D.D., Peret T.C., Burns C., Ksiazek T.G., Rollin P.E., Sanchez A., Liffick S., Holloway B., Limor J., McCaustland K., Olsen-Rasmussen M., Fouchier R., Gunther S., Osterhaus A.D., Drosten C., Pallansch M.A., Anderson L.J., and Bellini W.J., Science 300, 1394–1399, 2003. [DOI] [PubMed]
  6. Department of Communicable Disease Surveillance and Response. WHO Consensus document on the epidemiology of severe acute respiratory syndrome (SARS). http://www.who.cds/csr/gar/2003.11.
  7. Marra M.A., Jones S.J., Astell C.R., Holt R.A., Brooks-Wilson A., Butterfield Y.S., Khattra J., Asano, J.K., Barber S.A., Chan S.Y., Cloutier A., Coughlin S.M., Freeman D., Gim N., Griffith O.L., Leach S.R., Mayo M., McDonald H., Montgomery S.B., Pandoh P.K., Petrescu A.S., Robertson A.G., Schein J.E., Siddiqui A., Smailus D.E., Stott J.M., Yang G.S., Plummer F., Andonov A., Artsob H., Bastien N., Bernard K., Booth T.F., Bowness D., Czub M., Drebot M., Fernando L., Flick R., Garbutt M., Gray M., Grolla A., Jones S., Feldmann H., Meyers A., Kabani A., Li Y., Normand S., Stroher U., Tipples G.A., Tyler S., Vogrig R., Ward D., Watson B., Brunharm R.C., Krajden M., Petric M., Skowronski D.M., Upton C., and Roper R.L., Science 300, 1399–1404, 2003.
  8. Poon L.L., Chan K.H., Wong O.K., Yam W.C., Yuen K.Y., Guan Y., Lo Y.M., Peiris J.S. J. Clin Virol. 2003;28(3):233–238. doi: 10.1016/j.jcv.2003.08.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gao W., Tamin A., Soloff A., D’Aiuto L., Nwanegbo E., Robbins P.D., Bellini W.J., Barratt-Boyes S., Gambotto A. Lancet. 2003;362(9399):1895–1856. doi: 10.1016/S0140-6736(03)14962-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Enserink M. INFECTIOUS DISEASES: Clues to the Animal Origins of SARS. Science. 2003;300(5624):1351a–1351. doi: 10.1126/science.300.5624.1351a. [DOI] [PubMed] [Google Scholar]
  11. Eickmann M., Becker S., Klenk H.D., Doerr H.W., Stadler K., Censini S., Guidotti S., Masignani V., Scarselli M., Mora M., Donati C., Han J.H., Song H.C., Abrignani S., Covacci A., Rappuoli R. Science. 2003;302(5650):1504–1505. doi: 10.1126/science.302.5650.1504b. [DOI] [PubMed] [Google Scholar]
  12. Guan Y., Zheng B.J., He Y.Q., Liu X.L., Zhuang Z.X., Cheung C.L., Luo S.W., Li P.H., Zhang L.J., Guan Y.J., Butt K.M., Wong K.L., Chan K.W., Lim W., Shortridge K.F., Yuen K.Y., Peiris J.S., Poon L.L. Science. 2003;302(5643):276–278. doi: 10.1126/science.1087139. [DOI] [PubMed] [Google Scholar]
  13. Ng S.K. Lancet. 2003;362(9383):570–572. doi: 10.1016/S0140-6736(03)14121-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Stavrinides J., Guttman D.S., J. Virol. 78(l), 76–82, 2004. [DOI] [PMC free article] [PubMed]
  15. Chim S.S., Tsui S.K., Chan K.C., Au T.C., Hung E.C., Tong Y.K., Chiu R.W., Ng E.K., Chan P.Y., Chu C.M., Sung J.J., Tam J.S., Fung K.P., Waye M.M., Lee C.Y., Yuen K.Y., Lo Y.M. Lancet. 2003;362(9398):1807–1808. doi: 10.1016/S0140-6736(03)14901-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ruan Y.J., Wei C.L., Ee A.L., Vega V.B., Thoreau H., Su S.T., Chia J.M., Ng P., Chiu K.P., Lim L., Zhang T., Peng C.K., Lin E.O., Lee N.M., Yee S.L., Ng L.F., Chee R.E., Stanton L.W., Long P.M., Liu E.T. Lancet. 2003;361(9371):1779–1785. doi: 10.1016/S0140-6736(03)13414-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Snijder E.J., Bredenbeek P.J., Dobbe J.C., Thiel V., Ziebuhr J., Poon L.L., Guan Y., Rozanov M., Spaan W.J., Gorbalenya A.E. J. Mol. Biol. 2003;331(5):991–1004. doi: 10.1016/S0022-2836(03)00865-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Tsui S.K., Chim S.S., Lo Y.M. N Engl J Med. 2003;349(2):187–188. doi: 10.1056/NEJM200307103490216. [DOI] [PubMed] [Google Scholar]
  19. Zhong N.S., Zheng B.J., Li Y.M., Poon, Xie Z.H., Chan K.H., Li P.H., Tan S.Y., Chang Q., Xie J.P., Liu X.Q., Xu J., Li D.X., Yuen K.Y., Peiris, and Guan Y., Lancet 362, 1353–1358, 2003. [DOI] [PMC free article] [PubMed]
  20. Richter M., Can HIV AIDS Policy Law Rev 8(l), 14--19, 2003.
  21. Zambon M.C. J. Antimicrobial Chemother. 1999;44:3–9. doi: 10.1093/jac/44.suppl_2.3. [DOI] [PubMed] [Google Scholar]
  22. Bush R.M., Smith C.B., Cox N.J., Fitch W.M. Proc Natl Acad Sci, USA. 2000;97:6974–6980. doi: 10.1073/pnas.97.13.6974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Chinese SARS. Molecular Epidemiology Consortium, Science. 2004;303(5664):1666–1669. doi: 10.1126/science.1092002. [DOI] [PubMed] [Google Scholar]

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