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Biotech / Medical : SARS and Avian Flu -- Ignore unavailable to you. Want to Upgrade?

To: chomolungma who wrote (1173)	1/9/2004 11:15:58 AM
From: Henry Niman	Read Replies (1) \| Respond to of 4232

Here's the real deal on the SARS clock: >>In a statement Friday night, WHO said it wanted additional data and suggested further tests would be appropriate << I think WHO needs to be a bit more aggressive and transparent. The key to SARS is the sequence of the virus. Last year sequences were collected from patients who were infected in early February and later. Analysis of the sequence data was pretty straight forward and the subsequent collections generated a mutation clock, that defined the outbreak almost down to the day. The civet sequences provided a start point and generated this approximate clock. In late January / early February, the SARS CoV genome had already undergone 23 mutations (relative to the consensus civet sequence). These 23 mutations were in all human isolates from last year's outbreak. In addition to the 23 mutations in all isolates, there were 27 more loci that eventually mutated by the time SARS exploded at the Metropole Hotel. Thus, the clock from civet jump to international explosion was defined by 50 mutations. Here is the progression in February: 23 Found in all human isolates 25 The earliest isolate was GZ01 (the original sequence, not the revised GD01 sequence which has later mutations) - GZ01 did not have the 29 nt deletion - Isolated late January / early February 27 GZ43 - the additional 4 mutations not the same as the additional 2 in GZ01 indicating independent infections. GZ43 has 29 nt deletion and an adjacent 1 nt deletion All subsequent isolates (excluding GZ60 which was from another HCW in same hospital) had the 29 nt deletion (except GD01 which is supposed to be from same patient as GZ01) 33 GD01 is similar to GZ01 but has several later mutations, including ones just found in Beijing 44 CUHK-W1 Hong Kong patient who had visited Shezhen. Symptoms in Feb 44 BJ02 From pooled samples of early Beijing cases 45 BJ01/B03 Two isolates from Beijing index case 45 GZ50 Another early Guangzhou case 50 All isolates linked to Metropole Hotel, including all human isolates outside of mainland China On the animal side the sequence for these 50 mutations is: 0 SZ16 (masked palm civet) 0 SZ13 (raccoon dog) 1 SZ1 (masked palm civet) 4 SZ3 (masked palm civet) - This isolate also had 3 additional mutations found in human isolates - 2 found in GZ43 and 1 in CUHK-AG3 All of the above relate to last year's outbreak. Isolates after the Metropole Hotel continued to accumulate mutations (6 dozen found in at least 2 isolates), but these mutations were confined to geographical locations or known contacts (i.e. Singapore index case and her physician). Additional early isolates (like GZ60) not included because full sequence is not at GenBank. The above mutation lists makes two points. One shows the steady progression of these mutations in humans while another is the progression in animals. There are additional animal isolates from more recent collections and based on media reports, it sounds like these are more "humanized" than last year (i.e. they have more of the 50 mutations above (or possibly some of the later human mutations). There is only one human isolate and the S gene is said to be an exact match of one of the more "humanized" civets. This would indicate that the index case was infected with an isolate that is closer to SZ3 than SZ1. It would also indicate that fewer mutations are required this season to reach to 50 found in the Metropole Hotel isolates. All of the above data is at GenBank for all to see. Publication of the S gene sequence from the current index case would allow anyone who wants to look to see what TIME it is. Right now WHO seems to be working on what month it is. Anyone with a calendar can get that answer and it does not require additional lab data. It is also obvious that it is 2004 and WHO should be using the data base from sequences in 2003 to understand where the epidemic is this year, nit trying to figure out if it is or isn't back. The sequence of the index case as well as the corresponding sequence of this second case would go a long way towards seeing how these independent early cases are related, as well as where the re-emergence stood in late December, 2003 on the SARS CoV mutation clock.