Genomic Sequencing of a SARS Coronavirus Isolate That Predated the Metropole Hotel Case Cluster in Hong Kong

The epidemic of severe acute respiratory syndrome (SARS) swept across the globe, with reported cases in more than 30 countries. As of July 11, 2003, the number of reported probable cases was 8437, with 813 deaths (1). A novel coronavirus, SARS-CoV, was promptly implicated as the causative agent (2)(3)(4). Macaques infected with SARS-CoV subsequently developed respiratory symptoms and pathology similar to SARS patients, thus fulfilling the Koch postulates (5). Efforts in sequencing the viral genome promptly followed, and the genomic sequence revealed little homology to previously characterized strains of coronaviruses (6)(7). The complete genomic sequences of several SARS-CoV isolates have since been made publicly available (www.ncbi.nlm.nih.gov). Several sequence variations exist among isolates. In general, based on these sequence variations, the majority of the isolates can be segregated into two groups: isolates that were obtained from individuals who were epidemiologically linked to and those who were not linked to the Metropole Hotel in Hong Kong (8)(9)(10). Ruan et al. (10) compared the genomic sequences of 14 SARS-CoV isolates and suggested that a haplotype comprising four nucleotide positions, namely, 9404, 17564, 22222, and 27827 [GenBank accession no. AY274119 (7)], clearly defined two distinct genotypes. Isolates that were epidemiologically linked to the Metropole Hotel cluster have the configuration T:T:T:T, as opposed to the sequence C:G:C:C seen in the unassociated strains. (Note: The usage of the DNA-based code for the designation of SARS-CoV haplotypes does not imply that this virus possesses a DNA genome.) SARS was first reported in Guangdong Province, China, in November 2002 (11). Isolates that demonstrated the C:G:C:C haplotype were epidemiologically traceable to the early part of the epidemic (9). On the other hand, SARS …