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Biotech / Medical : Biotech Valuation -- Ignore unavailable to you. Want to Upgrade?

To: Biotech Jim who wrote (9943)	1/7/2004 5:11:49 AM
From: Henry Niman	Respond to of 52153

>> I wonder what the read error rate was<< I am only talking about shared polymorphisms. These are very rare and the chance that they pair up on a genome of almost 30,000 nucleotides is close to zero.

To: Biotech Jim who wrote (9943)	1/7/2004 5:20:34 AM
From: Henry Niman	Respond to of 52153

BJ, The direction of the transfer is difficult to determine, but some of the civets are quite "humanized". I haven't seen the latest data but SZ3 has 4 polymorphisms seen in all human isolates, two seen in an early health care worker (in Guangzhou), and one in a fatal Amoy Gardens case (these 7 polymorphisms are not in the other 3 animal sequences at GenBank) The linkage is quite strong and if it is because humans are infecting civets, then those animal sequences at GenBank link back to earlier cases (none have the 29 nt deletion, but virtually all human SARS from last season do (GZ01/GD01 is the only human isolate with the 29 nt). However, the animal isolates now are being reported as being more "humanized", which certainly sounds like humans infecting civets. Its probably a two way street (experimentally many species including domestic cats and ferrets) can be infected by fully mutated human isolates, including those with the 29 nt deletion), which is why the civets are being culled.

To: Biotech Jim who wrote (9943)	1/7/2004 6:11:31 AM
From: Henry Niman	Read Replies (1) \| Respond to of 52153

Here is an update on civet SARS CoV "humanization": Since there are now two SARS antibody positive cases in Guangzhou, and the report below suggests that the SARS CoVs in civets are becoming more "humanized", it is worth going over last season's data on "humanization" of civet SARS CoVs. There are 3 civet SARS CoV sequences on deposit at GenBank and they illustrate the process of humanization. All three isolates have the "wild type" version of 19 positions which are mutated in 100% of human isolates, so if these civets were infected by humans, they were infected by early cases (those infected before the isolates from the cases which showed symptoms in Feb 2003 or later). None of the isolates on deposit have the 29 nt deletion, which seems to have happened around the beginning of February 2003. GZ01/GD01 is the only human isolate with the 29 nt. However, the three civet isolates show three different levels of "humanization". SZ16 has none of the polymorphisms found in humans. The only shared polymorphism is C26523T, but it is shared with SZ13, which is from a raccoon dog and suggests SZ16 may have infected SZ13. Another civet isolate, SZ1, however, has a shared human polymorphism. C24566T is found in almost all human isolates (it is still wild type only in the earliest human isolates, GZ01, GD01, GZ43. GZ60. as well as the other animal isolates. The most "humanized" isolate is clearly SZ3. This isolate has four polymorphisms, T22220C, A23163T, T24383G, G28034G, which has been found in ALL human isolates (but not the other animal isolates). However, in addition to these 4 "human" changes, the isolate has three more than have a much more limited human distribution. 2 of them, T16521G and T17723C, are found in GZ43 (from a nurse treating patients in Guangzhou last January), while another, A28102C, is found in CUHK-AG3, a fatal Amoy Gardens case (there is some evidence that both of these sets of more limited "humanized" polymorphisms involved recombination, but that is another story. In any event, the report below suggests that recent animal isolates are even more "humanized", which would suggest that there are more of these mutations that previously were only seen in humans. One that jumps is out is the 29 nt deletion, but the detection of the 29 nt deletion in animal isolates has not been mentioned or confirmed. If it is in the later animal isolates, it would provide strong evidence for infection of civets by humans and the exact match of the S gene found in the current Guangzhou case with one of the more "humanized" civet isolates, suggests that the infections are going in both directions (humans infecting civets and civets infecting humans). >>Professor Yuen Kwok Yung, head of the microbiology department of the Hong Kong University's medical faculty, said recent samples of the Sars virus taken from the cats showed more similarities to the human form than samples taken from the animals during the last outbreak. 'There is some genetic evidence that this new virus from the civet cats... is moving towards the human Sars coronavirus,' said Prof Yuen, whose team identified the civet cat as the prime suspect of the source of the Sars epidemic in May last year. 'We fear that may mean higher transmissibility to humans. That looks a little sinister,' he told Reuters in an interview.<< Maybe the clock is not quite back to zero. Do any of the animal sequences have the 29 nt deletion? straitstimes.asia1.com.sg JAN 7, 2004 New virus may jump more easily to humans HONG KONG - Recent genetic studies in Hong Kong have detected small but significant changes in the Sars virus isolated from civet cats that suggest it may jump more easily to humans, a leading microbiologist said yesterday.