Molecular Advances in Severe Acute Respiratory Syndrome-associated Coronavirus (SARS-CoV)

Chow, Ken Yan Ching; Hon, Chung Chau; Hui, Raymond Kin Hi; Wong, Raymond Tsz Yeung; Yip, Chi Wai; Zeng, Fanya; Leung, Frederick Chi Ching

In coronavirus, variations in the spike protein can drastically affect viral entry, pathogenesis (94 ), antiviral immune response (29 ) , virulence (95 ), cellular (6 ), or even species tropism (7 ) . The S gene has been used as a target for genotyping most coronaviruses, like human coronaviruses (96 ) and IBV (97 ) . Study of the N-terminal region of the SARS-CoV spike protein produced similar conclusions by conventional epidemiology methods (98 ) . The investigation included the collection S1 gene sequences from SARS patients in Hong Kong and Guangdong during February-April 2003 mainly by direct sequencing of RT-PCR products derived from clinical specimens, and compared it phylogenetically to additional 27 other sequences available from GenBank. The majority of the Hong Kong viruses, including those from a large outbreak in a high-rise apartment block, Amoy Garden, clustered to a single index case that came from Guangdong to Hong Kong in late February ( Figure 3 ). Most of the viruses derived from Hong Kong patients belong to the same lineage with viruses derived from the Hong Kong index case. Outbreaks in Canada, Singapore, Taiwan and Vietnam were also derived from the SARS-CoV of the same initial virus lineage as judged from the same phylogenetic analysis. A number of viruses derived from the early patients were excluded from the major lineage and formed distinct cluster, implying multiple introductions of the virus have occurred, although these viruses did not caused large-scale outbreaks. Viral sequences identified in Guangdong and Beijing are genetically more diverse (1 , 98 ) , implying that the SARS-CoV has been circulating there for a while before the introduction to Hong Kong. The Hong Kong index case that initiated the first super-spreading incident to affect 12 other patients might be simply a matter of chance or the viruses found in that patient were contagious to initiate super-spreading events, but these still need further investigations. Apart from findings that indicate the possible transmission routes, transitional isolates that possess both the characteristics of two lineages were also identified. Ruan et al (99 ) and Tsui et al (100 ) performed similar analysis based on the comparison of full genome sequences of different SARS-CoV isolates. They independently identified some of the variations, as Guan et al (98 ) did. Chiu et al (101 ) have recently identified the nucleotide substitution in the S gene that is unique to the Taiwan isolates and was linked to the Hong Kong index case. Sequence comparison of the Amoy Garden isolates revealed no significant variations within the S1 gene, or across the whole genome, implying that other non-viral factors may contribute to the abnormal transmission and clinical presentation of SARS in this cluster of high-rise apartments (98 , 102 ) . In summary, the transmission route of the SARS-CoV in different countries and areas correlates well with the traditional epidemiological findings, implying the successful application of molecular epidemiological techniques in tracing the virus transmission history.