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


To: Biomaven who wrote (1149)1/6/2004 7:15:45 PM
From: Henry Niman  Respond to of 4232
 
Peter, Right now it looks like a re-run (assuming no fully mutated versions are floating around):

>>Dr. Yuen said that a genetic sequencing of samples from the man in Guangzhou who has SARS had found that the main "spike" protein was exactly identical, down to the last amino acid, to the new sublineage of the virus found in civet cats. Dr. Guan Yi, another Hong Kong University microbiologist, said that it was too soon to say whether the new sublineage was any more or less infectious or lethal in people than the SARS virus that spread last spring.<<

Although some are still questioning the seasonality of SARS, the above quotes certainly sound like a re-run of last year. Although there was some polymorphisms among the 3 civet isolates at GenBank, the isolates were clearly closer to each other than to the human isolates. Using the three civet sequences to define human mutations, the S gene had 13 positions that had change in all human isolates and another 9 positions that had changed in almost all human isolates.

Thus, it looked like the 9 positions had not quite had a chance to mutate when the initial SARS CoVs were isolated in Guangzhou last February, but by the time the virus emerged from the Metropole Hotel, all 22 positions in the S gene had mutated.

Interestingly, 99.4% of 3768 nucleotides in the S gene would also be approximately 22 differences. Thus, it seems that the isolate for this season's index case has reset the mutation clock, and as of Dec 16, 2003 all or almost all of these 22 positions were back to the wild type sequence defined by the consensus civet sequence.

The 100% identity quoted above may be for a civet slightly different than those deposited at GenBank, but they are probably pretty close and the sequence of the index case is revealing a replay of the SARS CoV genome at the beginning of last season's SARS outbreak.



To: Biomaven who wrote (1149)1/6/2004 7:53:39 PM
From: Henry Niman  Respond to of 4232
 
>>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.



To: Biomaven who wrote (1149)1/7/2004 1:32:13 PM
From: Henry Niman  Read Replies (1) | Respond to of 4232
 
Below the official Chinese news agency acknowledges that the second patient with SARS symptoms has SARS antibodies, but no longer has a fever. This second case some remarkably like the confirmed case. It will be interesting to see if any sequence data can be obtained from the second patient. The key question raised by these two unlinked cases which happened at about the same time, is how may SARS CoV infected people are there with even milder symptoms?

Last season the case fatality rate rose as did the mutations. The reliable of the reports have some question marks, but last year there were only 5 reported deaths among the first 305 cases, yielding a case fatality rate of 1.6%. By the time the epidemic emerged from the Metropole Hotel and spread internationally, the rate rose 10 fold. It was even higher in Mainland China and Taiwan, but then at the end of the epidemic, the rates reported by mainland China and Taiwan plummeted, to bring the worldwide rate below 10%. Moreover, after the fact Taiwan went back and reclassified 1/2 of the cases that were SARS CoV positive and called them SARS-CoV "related" and this dropped their case fatality rate even more. In fact they lowered it so much that the rate was lower for the SARS CoV positive suspect cases than the SARS CoV negative - they managed to show that SARS CoV infections saved lives!

In any event, regardless of the reliability of case fatality reports, the SARS CoV clearly accumulated mutations. There were 27 early mutations and the earliest isolated, GZ01, only had 2. Likewise another early isolate, GZ43, only had 4. By the time SARS emerged from the Metropole Hotel, all linked isolates (as well as all isolates outside of mainland China) had all 27 positions mutated (which was in addition to 23 mutations found in all human isolates).

This year the first sequence of the S gene is identical to a civet isolate. However, the isolate is more "humanized" indicating it already has some of the human mutations that were not found in animal isolates last year. Last year most of the mutations arose in February, March, and April. This year the earliest isolates seem to have more mutations than last season at this time. I'm sure that this year both patients and sequences will be closely monitored..

www1.chinadaily.com.cn

No symptoms from 2nd suspected case
( 2004-01-07 23:54) (China Daily)

The second suspected case of SARS, a female restaurant employee, has had no fever symptoms for eight consecutive days, local medical experts said yesterday.

The patient was exposed to the public for the first time by authorities on January 5.

She had tested positive for severe acute respiratory syndrome (SARS) antibody on her first test, said Guangzhou Respiratory Disease Research Institute Director Zhong Nanshan on Monday in Hong Kong.

More tests were to be conducted to decide whether she was in fact a suspected SARS case or not, Zhong added.

Tests have been conducted everyday, but the results remain unknown, said a source in provincial medical circles.