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

To: Amy J who wrote (1139)	1/4/2004 3:03:37 AM
From: Henry Niman	Respond to of 4232

>>How far away are scientists from a vaccine? << If the current case is what it seems to be, then making a vaccine will be much more difficult because there will be so many versions of the virus floating around, each capable of causing SARS and mutating further to evade the vaccine. It is looking more and more like efforts to nip the virus in the bud will fail. It seems to have jumped to humans via several species and can theoretically go back and forth, so a vaccine may be similar to a flu vaccine, requiring new versions each season. This of course is possible, but so far it looks like the virus is winning the race.

To: Amy J who wrote (1139)	1/4/2004 1:28:53 PM
From: Henry Niman	Respond to of 4232

The latest Reuters report includes several comments from groups analyzing rapidly evolving data, so right now its probably worthwhile going over what is known, based on multiple media sources. The sequenced virus is clearly a novel SARS CoV. The reported data covers 3768/3678 nucleotides in the S gene, 658/666 nucleotides in the M gene, and 1068/1269 nucleotides in the N gene. Thus, sequencing is complete in S, almost complete in M, and mostly complete in N (as of last week). In S the % homology with reported SARS CoVs is 98.8% to 99.4% and for M and N it is 99%. These numbers clearly show that a novel SARS CoV has been sequenced (the SARS CoVs from masked palm covets and a raccoon dog were approximately 99.8% homologous to human isolates and were 100% to the N gene in the vast majority of human isolates) and there are too many differences to be explained by sequencing errors. Moreover, the large number of differences rule out contamination of the patient's sample with a previously reported SARS CoV. If the rats in the apartment are indeed infected with a similar SARS CoV, then they theoretically could contaminate the sequence in the patient's samples if infected rat tissue was in the first lab reporting the PCR positive. However, this explanation seems unlikely because the patient is reported to have antibodies to SARS CoV and recent reports suggest he has low levels of neutralizing antibodies. Since the new virus has not been isolated, the target for the antibody tests would be a previously isolated SARS CoVs and the sequencing data would indicate that this target SARS CoV would have 22-44 nucleotide differences in the S gene, so the titer of neutralized antibodies against the lab SARS CoV would almost certainly register at a significantly reduced level. Thus the fact that neutralizing antibodies were detected at all, using a relative early serum sample, strongly implicates the novel SARS CoV in the SARS symptoms seen in the patient. The questions that remain fairly open are the direction of the infection and the relationship of the current SARS symptoms to those seen last March in the Guangzhou index case. The current isolate is quite distinct from all other isolates, but it also has not been successfully cultured. Currently, the vast majority of the SARS CoV sequences at GenBank are from cultured SARS CoV isolates, so if the current variant does not grow well in culture, then it may have been missed earlier. Alternatively, in the past 9 months the virus may have significantly changed, either silently in humans or in an animal reservoir, such as rats. Some of these questions can be answered by the current sequence itself, but sequencing of rat isolates as well as more patient's samples (including March samples from the current Guangzhou index case), will go a long way towards determining the clinical relevance of this novel SARS CoV.

To: Amy J who wrote (1139)	1/5/2004 12:55:09 AM
From: Henry Niman	Read Replies (1) \| Respond to of 4232

Is the cat already out of the bag? Mainland China is now playing civet catch-up, but there are some indications that they may be late. Last season SARS CoVs were not only isolated from 6 civet cats, but also one raccoon dog. The sharing of a mutation C26523T between a masked palm civet isolate (SZ16) and the raccoon dog isolate (SZ13), suggests that the civet may have infected the raccoon dog. The index case in Guangzhou for this season seems to trace back to another lineage with linkage to the masked palm civets and Beijing has ordered the slaughter of 10,000 civets. However, if the 99% homology in the N gene of the latest isolate means that there are 10-11 mutations in the 1068 nucleotides sequenced, then it seems likely that yet another animal has jumped into the line of transmission. The N gene is well conserved and most human isolates from last seasons had 100% identity with N gene in the masked palm civet isolate. None had anything like 10-11 mutations. If the current isolate really has that many mutations, then it seems likely that this case was infected by SARS CoV from another species, possibly coronavirus positive rats. Previously detected coronaviruses in rats (which were class II) had little homology with SARS CoVs. However, these rats could conceivably have a SARS CoV-like infection (a standard SARS CoV test would not detect the class II rat CoV, which is most closely related to murine hepatitis virus and more distantly related to human OC43 coronavirus which causes colds in humans). If the rats in the apartment were tested, it seems likely that the test would have been for SARS CoV and unlikely that such a test would detect a class II rat coronavirus. Thus, the positive coronavirus test clearly raises the possibility that SARS CoV infected rats actually caused this infection and the rats may in fact have been oreviously infected with SARS CoVs from civets. In the Amoy Gardens outbreak, SARS CoV was found in 4 cats, 1 dog, and 4 rats and lab experiments have shown that cats and ferrets can transmit the SARS CoV to cage mates. At this point more data is required on the rats in the apartment as well as others who have SARS-like conditions, now and in the past, because as has been shown in earlier tests on this Guangzhou index case, the mutated SARS CoV is not always detected by the current SARS CoV tests. China Orders 10,000 Civet Cats Killed In Guangdong DOW JONES NEWSWIRES BEIJING (AP)--China Monday ordered some 10,000 civet cats in wildlife markets killed in its southern province of Guangdong after genetic tests suggested a link to a suspected SARS case. All wildlife markets in Guangdong were ordered to close, Feng Liuxiang, deputy director of the province's health department, said on national television. Civets are served in wild game restaurants in Guangdong. The announcement came after researchers at Hong Kong University said they found similarities between a virus found in the cats and in a suspected SARS patient in Guangdong, suggesting the disease might have jumped from animals. "We will take resolute measures to close all the wildlife markets in Guangdong and to kill the civet cats," Feng said on the national noon newscast of China Central Television.