Molecular advances in the cell biology of SARS-CoV and current disease prevention strategies

Stark, Caren J; Atreya, CD

RNA viruses utilize a variety of mechanisms to exchange their genetic repertoire. The viral RNA dependent RNA polymerases (RdRP) have a built in error rate that allows diversification of the genomic sequence as replication proceeds. Estimates put the error rate of an RdRp at 10 -3 to 10 -5 per nucleotide [30] . Coronaviruses also undergo high rates of RNA recombination, providing an additional mechanism by which the viruses can rapidly amplify genomic diversity. The SARS-CoV polymerase gene has a recombination breakpoint, suggesting multiple genetic origins for this molecule. [31] . These evolutionary mechanisms may have facilitated the adaptation of the animalborne SARS-CoV ancestor to the human host, suggesting that such events in the future could lead to a virus with increased pathogenicity for humans or one capable of infecting multiple species. Recent evidence indicates that the human-adapted SARS virus has crossed into another species. Sequence and epidemiological analyses revealed that a SARS-CoV isolated from a pig was derived from a human strain. Complete nucleotide sequencing of the pig virus isolate (designated TJF) and an S gene-based phylogenetic tree analysis revealed a closer relationship with human SARS-CoV isolates than with animal coronaviruses [32] .