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Published online on February 11, 2004, 10.1073/pnas.0307904100

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Microbiology
Characterization of severe acute respiratory syndrome coronavirus genomes in Taiwan: Molecular epidemiology and genome evolution

Shiou-Hwei Yeh *{dagger}, Hurng-Yi Wang {ddagger}, Ching-Yi Tsai {dagger}, Chuan-Liang Kao §, Jyh-Yuan Yang ¶, Hwan-Wun Liu ||, Ih-Jen Su ¶, Shih-Feng Tsai *, Ding-Shinn Chen {dagger}**{dagger}{dagger}{ddagger}{ddagger}, Pei-Jer Chen {dagger}**{dagger}{dagger}{ddagger}{ddagger}, the National Taiwan University SARS Research Team §§, Ding-Shinn Chen a,b, Yuan-Teh Lee c,d, Che-Ming Teng e, Pan-Chyr Yang b, Hong-Nerng Ho f, Pei-Jer Chen g, Ming-Fu Chang h, Jin-Town Wang i, Shan-Chwen Chang b, Chuan-Liang Kao j, Wei-Kung Wang i, Cheng-Hsiang Hsiao k, and Po-Ren Hsueh l

*Division of Molecular and Genomic Medicine, National Health Research Institutes, Taipei 115, Taiwan; {dagger}Hepatitis Research Center and **Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan; {ddagger}Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan; §Department of Medical Technology, National Taiwan University, Taipei 100, Taiwan; Center for Disease Control, Taipei 115, Taiwan; ||Institute of Preventive Medicine, National Defense Medical College, Taipei 237, Taiwan; and {dagger}{dagger}Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 100, Taiwan; Offices of athe Dean and eResearch and Development, and Departments of bInternal Medicine, hBiochemistry and Molecular Biology, iMicrobiology, jMedical Technology, kPathology, lLaboratory Medicine, and gGraduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 100, Taiwan; and cOffice of the Superintendent and Departments of dInternal Medicine and fMedical Research, National Taiwan University Hospital, Taipei 100, Taiwan

Communicated by Robert H. Purcell, Bethesda, MD, November 27, 2003 (received for review June 28, 2003)

Since early March 2003, the severe acute respiratory syndrome (SARS) coronavirus (CoV) infection has claimed 346 cases and 37 deaths in Taiwan. The epidemic occurred in two stages. The first stage caused limited familial or hospital infections and lasted from early March to mid-April. All cases had clear contact histories, primarily from Guangdong or Hong Kong. The second stage resulted in a large outbreak in a municipal hospital, and quickly spread to northern and southern Taiwan from late April to mid-June. During this stage, there were some sporadic cases with untraceable contact histories. To investigate the origin and transmission route of SARS-CoV in Taiwan's epidemic, we conducted a systematic viral lineage study by sequencing the entire viral genome from ten SARS patients. SARS-CoV viruses isolated from Taiwan were found closely related to those from Guangdong and Hong Kong. In addition, all cases from the second stage belonged to the same lineage after the municipal hospital outbreak, including the patients without an apparent contact history. Analyses of these full-length sequences showed a positive selection occurring during SARS-CoV virus evolution. The mismatch distribution indicated that SARS viral genomes did not reach equilibrium and suggested a recent introduction of the viruses into human populations. The estimated genome mutation rate was {approx}0.1 per genome, demonstrating possibly one of the lowest rates among known RNA viruses.

{ddagger}{ddagger}To whom correspondence should be addressed at: Hepatitis Research Center, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei 100, Taiwan.

§§The National Taiwan University SARS Research Team:

E-mail: dschen{at}ha.mc.ntu.edu.tw, peijer{at}ha.mc.ntu.edu.tw.

www.pnas.org/cgi/doi/10.1073/pnas.0307904100
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