《资治通鉴》评说
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这几天美国政府管制科学论文发表，限制禽流感研究论文的刊登。许多媒体访谈和报道，说禽流感武器化就差一步，而且这一步很容易。这些报道称禽流感只要基因工程改为一般的流感传染途径，即可杀死60%的人口。
有文章认为1997禽流感爆发是人为基因工程的结果。以前中国每年春节鸡瘟，从来不会传染给人，按照下边文章的观点，鸡瘟传染给人是基因工程实验室做出来的。这个基因工程成功地在鸡瘟病毒中植入人流感病毒基因，使得禽流感得以从禽畜传染给人，只要给这些病毒加入人与人之间的传染基因，即可成为大规模杀伤武器。而这一步技术上已经不是问题，所以美国政府检查和禁止禽流感科学论文的发表。
1. Novel H1N1 is a man-made.
Yes.
In general influenza A virus consists of 8 genes. Influenza virus evolves to be able to adapt to new host. The evolution can happen in several way: by exchanging one or more complete genes (for example avian virus switching gene with human virus), called as reassortment; or only changing partial gene(s), called as recombination.
In the case of novel H1N1, this virus consists 8 genes mixed of avian, swine and human type influenza A virus. So, this is a reassortant virus.
Adaptation can occur too. This means, the virus makes small change (sometime only one amino acid change) but can make a complete adaptation to the new host. For example, if we passage human virus into eggs, the virus will make small mutation after several passage and will be reach efficiency to infect eggs (means, able to infect new host, in this case avian host). This is why Adrian Gibbs once said that novel H1N1 was a lab strain. Because he found a specific amino acid which might refer to the consequence of several passage in eggs. Vaccine industry usually amplify virus by isolating it into eggs, and after several passages this mutation can be found.
Mutation takes time to occur, up to the rate of amino acid substitution. For example, for HA gene, duck virus' HA has substitution rate about 3 x 10e-4 per site per year which is slower compare to human and swine HA (about 10e-3 per site per year). If total nucleotide number in influenza A virus HA is 1,700, then it takes 3 years for making single changes in duck virus, or 1.7 year in the case of human and swine virus. In instance, a complete gene mutation can take thousand of years to be established.
I read a paper of Suzuki and Nei, 2002 (Mol. Biol.Evol. 19(4): 501-509 2002), they mentioned that the divergence between subtypes of influenza A virus HA genes was estimated to be about 2000 years ago.
It means, duck virus (as well as other waterfowls) tends stable compare to human and swine virus. Well, waterfowls are the natural host of influenza virus, so it's more constant. But when the virus jumps into new host (like chickens, pigs or human), the substitution rate will accelerate to adapt well in the new host. New adaptation will cause rapid mutation, but it will be slowing down after time. We see the same pattern in the case of novel H1N1. The novel H1N1 shows stable sequences since its first outbreak. Usually I compare the later sequence with first California sequence, and in general the virus is quiet stable. Some important mutations are detected, though. Such as, amino acid no 627 of PB2 gene, which is related to mammalian adapted strain, found in a Shanghai isolate. Also, a mutation in amino acid no 275 of NA gene, which is related to oseltamivir resistant strain, were found in one Canada and one Japan isolates. Some other 'silent' mutations (silent means no amino acid changes) can be found in other isolates, but still I think that the virus is quiet stable up to now.
Now I'm talking about the reassortment (like novel H1N1 virus). It may take shorter time to occur compare to amino acid substitution/adaptation/mutation. If you take a look to the genotype map and the phylogenetic trees that I sent you previously, the novel H1N1 virus consists of avian, human and swine virus genes. The theory is maybe an individu got infected by avian, human and swine virus at the same time, and the viruses exchanged genes inside the body, creating a new virus having mixed genes and spreading. Theoritically it is possible to occur. But how?
What we need:
a. A host. The host should have efficient receptor for those three different derived hosts. So far, human virus tends to infect human, because it suits to human receptor. Avian virus tends to infect birds, because it suits to bird receptors. Pigs have both human and avian type receptors, so it is said that pig is the 'mixing vessel'. However, some researchers tried to prove this mixing vessel theory by trying to infect pigs by human and avian viruses to create reassortant. They didn't make it.
There are some reports that showed the finding of human and bird influenza virus in pigs. So it is easy for pigs to get infected by human and birds, but lack of report showing that pigs shed the reassortant virus and infect new host.
So,where is the responsible host? The first novel H1N1 virus was found in human. After that what I know is some pigs and turkey were transmitted this virus by farm workers. Not the opposite. Until now, no one can give evidence of this reassortant theory.
b. Reassortant needs ancestor viruses
Aain, if you check the phylogenetic tree. It shows, the NA and M genes derived from avian virus; PB1 from human H3N2; other genes (PB2, PA, HA, NP, NS) from swine triple reassortant, Swine H1N2 and Eurasian Swine (H1N1/H3N2). The triple reassortant swine I mentioned before, actually derived from human H3N2 which infected pigs, and has been circulating in North America at least for 20 years.So that people say it as swine virus (well, I'm still saying it's actually human virus).
Funny thing is those suspected ancestors are coming from pretty old isolates.
A paper written by Smith et al., 2009, is saying that the NA gene comes from 1996-2001 isolate (I suspect this as the NA gene of H5N1, the isolate year confirmed this). The M genes from 1990-1993 isolates, the others even pretty old, somewhere between 1979 to 80's isolates. The author argued that the virus had been detected for over 20 years without being detected???
Come on, people is doing surveillance everywhere, but no one detected the virus for 20 years??
A reassortant can happen very quick. If it was already there before, it must have been spreading long time ago, is it in pigs or human or else.
But again where's the evidence??
Still they said the virus is circulating in pigs, but no one can prove it.
We can make a story about this: there is a pig, got infected by human and avian virus from 10 to 20 years ago isolates. And creating a very good virus with effective transmissibility. Please, how can you find those pretty old isolates circulating?? Doesn't make sense.
c. Reassortant needs to be facilitated.
Now tell me Robert. How can you mix avian, human and pig virus at one time? The viruses must come from Europe, America and Asia, without being noticed? And luckily you can make completely efficient newly generated virus?
Simply for me, the virus was emerged suddenly in Mexico. I can't explain how. I wish I could. For me as a virologist, it's impossible. In the other hand, technology can create any kind of virus you want.
引用资料来源：
http://www.freepeoples5thestate.com/2011/12/breaking-government-admits-h5n1.html
参考链接：
禽流感生化武器
管制禽流感病毒研究文章发表
