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May 9, 2003

Commentary -- Comparative analysis of the SARS coronavirus genome: a good start to a long journey 

Earl G Brown, Jason A Tetro 

Severe acute respiratory syndrome (SARS) is the latest in a long list of emerging infectious diseases to gain the attention not only of the scientific community but also of the general public. SARS is characterised by symptoms that include a temperature over 38°C, dry cough, myalgia, and mild sore throat, which progresses to atypical pneumonia. The disease is unusual in its high morbidity and mortality rates; and it mimics and indeed rivals the 1918 influenza pandemic, which still stands as the worst pandemic in history. More disturbingly, SARS seems to transmit through direct contact and extreme infection-control measures are thus needed in affected areas. 

Comparative full-length genome sequence analysis of 14 SARS coronavirus isolates and common mutations associated with putative origins of infection 

YiJun Ruan, Chia Lin Wei, Ling Ai Ee, Vinsensius B Vega, Herve Thoreau, Se Thoe Su Yun, Jer-Ming Chia, Patrick Ng, Kuo Ping Chiu, Landri Lim, Zhang Tao, Chan Kwai Peng, Lynette Oon Lin Ean, Ng Mah Lee, Leo Yee Sin, Lisa F P Ng, Ren Ee Chee, Lawrence W Stanton, Philip M Long, Edison T Liu 

Summary 

Background The cause of severe acute respiratory syndrome (SARS) has been identified as a new coronavirus. Whole genome sequence analysis of various isolates might provide an indication of potential strain differences of this new virus. Moreover, mutation analysis will help to develop effective vaccines. 

Methods We sequenced the entire SARS viral genome of cultured isolates from the index case (SIN2500) presenting in Singapore, from three primary contacts (SIN2774, SIN2748, and SIN2677), and one secondary contact (SIN2679). These sequences were compared with the isolates from Cana (TOR2), Hong Kong (CUHK-W1 and HKU39849), Hanoi (URBANI), Guangzhou (GZ01), and Beijing (BJ01, BJ02, BJ03, BJ04). 

Findings We identified 129 sequence variations among the 14 isolates, with 16 recurrent variant sequences. Common variant sequences at four loci define two distinct genotypes of the SARS virus. One genotype was linked with infections originating in Hotel M in Hong Kong, the second contained isolates from Hong Kong, Guangzhou, and Beijing with no association with Hotel M (p<0·0001). Moreover, other common sequence variants further distinguished the geographical origins of the isolates, especially between Singapore and Beijing. 

Interpretation Despite the recent onset of the SARS epidemic, genetic signatures are emerging that partition the worldwide SARS viral isolates into groups on the basis of contact source history and geography. These signatures can be used to trace sources of infection. In addition, a common variant associated with a non-conservative aminoacid change in the S1 region of the spike protein, suggests that immunological pressures might be starting to influence the evolution of the SARS virus in human populations. 

Published online May 9, 2003 

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