Here is a bit more analysis on the sequence information released showing that the Guangzhou isolated is about 99% homologous to other SARS CoVs in the S, M, and N genes.
The data essentially eliminates the possibility that the sequence is from lab contaminants because contaminants would produce exact matches (there could be a few differences due to sequencing errors, but those difference would be far less than the 1% reported). The reported numbers indicate that there are 22 or 23 differences in the S gene (relative to the closest Genbank match), 6 or 7 differences in the M gene, and 10-11 differences in the N gene (these assume that the reported differences are not due to major insertions or deletions, but those types of changes generally have not been found in these genes).
Thus the 99% homology would indicate that the sequence is not a lab contaminant and the virus is in the SARS CoV group of coronaviruses (other animal coronavirus generally have 20-30% sequence homology).
However, although the sequence is from a SARS CoV, the number of differences is on the high side, raising the distinct possibility that the virus came from a reservoir other than a masked palm civet. Comparison of the civet sequences to human sequences shows that most of the differences are concentrated in the S gene. The civets have 13 S gene polymorphisms that are found in 100% of the reported human isolates. There are 9 more polymorphism that are changed in almost all human isolates and 13 more found scattered in smaller regionally linked isolates. The new Guangzhou sequences has 22-23 changes relative to other SARS CoVs. If it came via civets, it would have the 13 polymorphisms found in all human isolates, so an additional 22-23 is quite a few. Some of these may be unique (the above changes did not include unique changes - all changes in human SARS CoVs described above were found in 2 or more isolates), so it is possible that the new isolate was linked to the civets, but just had quite a few more changes than other isolates.
However, the M and N genes are much more conserved in the SARS CoV sequences at Genbank, and differences in these genes raise the possibility that the recent isolate has a different animal reservoir. In the N gene there are no differences between the civet and human sequences that are widespread. There are 3 differences that are found in a small number of human isolates. The new Guangzhou sequence however appears to have 10-11 changes, which is much higher than any reported human SARS CoV. Thus it is these differences in the N gene that raise the possibility that the new Guangzhou sequence is actually a VERY closely related SARS CoV cousin.
One of the key questions about the current case relates to the source of the infection. The index case was reported to have had suspect SARS last March, but was not diagnosed with probable SARS. Thus, the two SARS-like conditions may have been unrelated. However, it seems possible that the SARS CoV partially sequenced was the same virus that caused the earlier symptoms, but the 1% difference made it more difficult to lab confirm the earlier suspect SARS condition. If the virus was not completely eliminated, then the current pneumonia could represent an re-activation of the virus.
The full sequence, or even the actual sequence completed thus far, will more precisely define the above possibilities, but at this time it seems clear that the Guangzhou patient was infected with a SARS CoV whose origin is not yet well defined. |
