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Variants Of SARS Virus Gives Clues To Origin Of Infection

May 08, 2003

A genetic study of the SARS virus fast-tracked for publication on THE LANCET's website-www.thelancet.com-gives an insight into the molecular behaviour of the novel coronavirus responsible for SARS. Comparison of a virus isolate from Singapore with isolates from other countries where SARS has struck suggests that there are main components of the virus which remain unchanged as infection has spread across different countries, although specific changes to the genetic structure of the virus provide clues to the origin of the infection.

The cause of severe acute respiratory syndrome (SARS) has been identified as a new coronavirus (SARS-CoV). A characteristic of RNA viruses (which includes SARS-CoV) is the high rate of genetic mutation, which leads to the evolution of new viral strains and is a mechanism by which viruses escape host defences. Therefore, from a public-health perspective, understanding the mutation rate of the SARS virus as it spreads through the population is important. Furthermore, the genetic mutability of SARS-CoV would also have an effect on the development of broadly effective vaccines.

Edison Liu from Singapore's Genome Institute and colleagues isolated and sequenced the entire SARS viral genome of cultured isolates from an index case in Singapore, from three primary contacts, and one secondary contact of the index patient. These sequences were compared with virus isolates from Canada, Hong Kong, Hanoi (Vietnam), Guangzhou, and Beijing (China).

129 sequence variations were identified among the 14 isolates, with 16 recurrent variant sequences. Analysis of the common variant sequences showed four parts of the genome that defined two distinct genotypes of the SARS virus: One genotype was linked with infections originating from the Metropol Hotel in Hong Kong; the second contained isolates from Hong Kong, Guangzhou, and Beijing (not associated with the Metropol Hotel). Four other common sequence variants seemed to distinguish the geographical origins of the isolates, especially between Singapore and Beijing.

Edison Liu comments: "The SARS viral epidemic has placed a substantial strain on the health and economic status of nations. Understanding the nature of this virus and deriving methods to control the epidemic are very important. Our results show several molecular facets of the SARS coronavirus pertinent to public-health management of this epidemic. Its novelty as a human pathogen suggests that most populations might be immunologically naive to its infection. The discovery of genotypes linked to geographic and temporal clusters of infectious contacts suggests that molecular signatures can be used to refine contact histories."

Earl Brown and Jason Tetro from the University of Ottawa, Canada, state in an accompanying Commentary: "Although there are a handful of mutations between isolates, the observed mutations may be due to adaption in culture because most are unique to each isolate. The results suggest a remarkable genetic conservation of the virus since the outbreak was first documented in February, 2003. Wide experience with the evolution of influenza A virus shows that such end-of-lineage changes are due to mutations selected in laboratory culture and, in this study, most of the mutations in the SARS-CoV sequences probably represent adaption to Vero cells during propagation before sequencing. It can therefore be concluded that as the virus passes through human beings, SARS-CoV is maintaining its consensus genotype and is thus well adapted to the human host. Unfortunately, this conclusion means that SARS-CoV is not likely to change rapidly and thus may not readily mutate to a benign infection, as is the hoped for eventuality seen in most other epidemics."

Lancet