SARS - Canada - The Genome Sequence of the SARS-Associated...

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/ / 1 May 2003 / Page 1/ 10.1126/science.1085953 We sequenced the 29,751-base genome of the severe acute respiratory syndrome (SARS)–associated coronavirus known as the Tor2 isolate. The genome sequence reveals that this coronavirus is only moderately related to other known coronaviruses, including two human coronaviruses, HCoV-OC43 and HCoV-229E. Phylogenetic analysis of the predicted viral proteins indicates that the virus does not closely resemble any of the three previously known groups of coronaviruses. The genome sequence will aid in the diagnosis of SARS virus infection in humans and potential animal hosts (using PCR and immunological tests), in the development of antivirals (including neutralizing antibodies), and in the identification of putative epitopes for vaccine development. An outbreak of atypical pneumonia, referred to as severe acute respiratory syndrome (SARS) and first identified in Guangdong Province, China, has spread to several countries. The severity of this disease is such that the mortality rate appears to be ~3 to 6%. A number of laboratories worldwide have undertaken the identification of the causative agent ( 1, 2 ). The National Microbiology Laboratory in Canada obtained the Tor2 isolate from a patient in Toronto, and succeeded in growing a coronavirus-like agent in African Green Monkey Kidney (Vero E6) cells. This coronavirus has been named publicly by the World Health Organization and member laboratories as “SARS virus” (press release issued by WHO April 16, 2003) following tests of causation according to Koch’s postulates, including monkey inoculation ( 3 ). This virus was purified and its RNA genome extracted and sent to the British Columbia Centre for Disease Control in Vancouver for genome sequencing by the Genome Sciences Centre at the BC Cancer Agency. The coronaviruses are members of a family of enveloped viruses that replicate in the cytoplasm of animal host cells ( 4 ). They are distinguished by the presence of a single-stranded plus sense RNA genome approximately 30 kb in length that has a 5´ cap structure and 3´ polyA tract. Upon infection of an appropriate host cell, the 5´ most open reading frame (ORF) of the viral genome is translated into a large polyprotein that is cleaved by viral-encoded proteases to release several nonstructural proteins including an RNA-dependent RNA polymerase (Rep) and an ATPase helicase (Hel). These proteins in turn are responsible for replicating the viral genome as well as generating nested transcripts that are used in the synthesis of the viral proteins. The mechanism by which these subgenomic mRNAs are made is not fully understood, however recent evidence indicates that transcription regulating sequences (TSRs) at the 5´end of each gene represent signals that regulate the discontinuous transcription of subgenomic mRNAs (sgmRNAs). The TRSs include a partially conserved core sequence (CS) that in some coronaviruses is 5´-CUAAAC-3´. Two major models have been proposed to explain the discontinuous transcription in
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SARS - Canada - The Genome Sequence of the SARS-Associated...

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