Forum: New Dominant H 5 N 1 Strain in China

I finally got round to writing up this paper Emergence and predominance of an H5N1 influenza variant in China, Smith et al, PNAS, Oct 2006

ABSTRACT: The development of highly pathogenic avian H5N1 influenza viruses in poultry in Eurasia accompanied with the increase in human infection in 2006 suggests that the virus has not been effectively contained and that the pandemic threat persists. Updated virological and epidemiological findings from our market surveillance in southern China demonstrate that H5N1 influenza viruses continued to be panzootic in different types of poultry. Genetic and antigenic analyses revealed the emergence and predominance of a previously uncharacterized H5N1 virus sublineage (Fujian-like) in poultry since late 2005. Viruses from this sublineage gradually replaced those multiple regional distinct sublineages and caused recent human infection in China. These viruses have already transmitted to Hong Kong, Laos, Malaysia, and Thailand, resulting in a new transmission and outbreak wave in Southeast Asia. Serological studies suggest that H5N1 seroconversion in market poultry is low and that vaccination may have facilitated the selection of the Fujian-like sublineage. The predominance of this virus over a large geographical region within a short period directly challenges current disease control measures.

The main points are:

• samples from poultry markets July 2005-June 2006 in 6 provinces showed 2.4% positive for H5N1
• chicken 0.5%, duck 3.3%, goose 3.5%
• this is up from the year before: overall 0.9%, chicken 0.2%, duck 1.3%, goose 2.0%
• H5N1 in chickens are generally isolated in winter, but year-round in duck and goose
• whereas H5N1 were isolated in chickens in 4 winter months before, now they are found in 11 out of 12 months.

The extension of the virus in poultry is more obvious on this chart

Of these isolates, previously there was a variety of different strains ie multiple sublineages. Since last winter, these have been overtaken by one new strain, called ‘Fujian-like’ sublineage.

Thank you Anon_22 for supplying all the information above.

Do you have the Journal of Virology, Nov. issue, with the article referred to-

deadly gene in H5N1

“Only chickens infected with the modified virus containing the highly pathogenic gene died. The other chickens had no signs of disease, the scientists wrote in the November issue of the Journal of Virology.

“Now that we know the special role of the (highly pathogenic) NS1 gene, we can think about developing a vaccine,” Bu said, adding that a vaccine which neutralizes the gene known as NS1 could be quickly designed.”

In addition, all 5 of the recent human cases with samples available were from the new strain. Below is a map of the provinces of China which is useful for this purpose. The poultry isolates studied were collected from Fujian, Guangdong, Guangxi, Guiyang, Hunan, and Yunnan, whereas the human samples were from 1 each from Guangdong, Guangxi, Zhejiang, and 2 from Anhui.

What is the anticipated impact from this new strain?

anon_22:

Can you clarify why they are calling this the “new” strain, rather than simply just the “newly dominant” strain, which would seem to be a more accurate description.

Many thanks for the summary.

There are 21 confirmed cases listed for China from the WHO, of which the retrospective one from 2003 I’m not including in this discussion (in relation to this new strain). The rest are all within the last year, with the first cases reported in November 2005.

The distribution of cases are 1 each from Xinjiang, Hubei, Shanghai (migrant), Jiangxi, Liaoning, and Guangxi. 2 each from Guangdong, Fujian, Hunan, and Zhezhiang, and 3 each from Sichuan and Anhui.

Apart from the 2 cases from Xinjiang and Liaoning, the rest are ‘concentrated’ in the more developed parts of China. I put the word ‘concentrated’ in quotes because China is so big that we are actually talking about a very large area. But I do want to say that these do seem to be grouped together geographically.

We can’t really draw any conclusions from these, as the data is so scant and the area is so big, but if the poultry and human sequences match (and they do), and if the 5 samples are representative of the rest of the human cases, (which we don’t know), and the new strain is now in 95% of the positive poultry samples (which we do know about), at least in the south, it would seem to me that this is a sign of a strain which is dominating avian infections for sure, and may be dominating human infections.

Pixie – at 16:14

Can you clarify why they are calling this the “new” strain, rather than simply just the “newly dominant” strain, which would seem to be a more accurate description.

No, it is a new strain, which very quickly became dominant.

The ‘prototype’ of this strain was first isolated in March 2005, and started a distinctly new sublineage on phylogenetic analysis. All those strains that belong on that sublineage are isolates from China since that time, but most markedly in the last few months. It is now also found in Hong Kong, Malaysia, Laos, and Thailand.

As for the significance, there are several issues to consider. Note that much of this is based on so little information that they verge on speculation, but I will attempt it anyway:

1) If you look at the first chart, with the increase in isolates in poultry, combine with the fact that seroconversion after vaccination is very low, (16%), then vaccination is not controlling the spread in poultry. However, bear in mind that we don’t know what the incidence of poultry infection might be without vaccination. It could be that vaccination is partly but not totally effective in controlling (ie reducing the incidence) of poultry infections.

2) Since ducks and geese are more frequently positive than chickens, and since the former are far more often asymptomatic with or without vaccination, it becomes even harder to judge from the farmers point of view whether they are getting value for money ie vaccinating to prevent economic loss, irrespective of disease control.

Unless, of course, the virus changes its behaviour in domestic ducks (as opposed to wild), which it has been known to do.

(I’m tempted at this point to stop and just type, its a mess, no one can analyse anything!)

3) One thing is for sure. If we were worried about multiple sublineages before, (and I was), then a single dominant strain with the almost complete disappearance of the other strains worrys me even more. This is because if we go back to basic virology, when you consider transmission, whether b2h or h2h, the virus needs a lot more than entering a host, binding to receptors, and entering the cells. It needs to survive the host immune response, then transmit to the next host. This ‘fitness’ issue is very important but may be difficult to quantify, except when you see this happening. One might say here that this virus appears to be very fit in birds. But is it likely to be similarly fit in humans? We don’t know. I suspect we won’t know until (or unless!) we see h2h.

What would be most useful to know at this point would be the sequences from the other human cases, more than anything else. Cos if we see that human infections are mostly caused by this strain (let alone only caused by this strain), that may give us a small indication of its likely fitness in humans. Even then, we still can’t say that this is likely to become a pandemic virus, cos, well, we don’t know until we know.

But what would really be worrying would be a combination of clusters and dominance of this strain in human infections.

I don’t know if this makes any sense. As I said, we are building on very little information, but what information we do have is certainly very significant.

would you say this is BAD news? or VERY bad news?In you best assesment. Thank you.

moderately BAD news.

OTOH, I’m used to bad news by now, so my calibration may be different from yours.

What I would say is this. Does this mean this is likely to be a pandemic virus? We don’t know. Are we more likely to have a pandemic because of this strain? I would like to see virulence studies in laboratories, at least, to observe how it behaves in mammals.

But it does confirm my original concern a while back, when everyone was worried about Indonesia and focusing on that, and I was saying, look, new strains are being formed in China all the time, and that is another likely source of a pandemic virus, not just Indonesia.

The other thing that I would like to know is what is the relative percentage of positives from tracheal vs cloacal and fecal samples. The data might be in the supplementary online material but I can’t get it at this moment.

According to Dr. N, at last count, there are at least 4-strains/Clades/sub-Clades, capeable of “walking off the plane” and starting a pandemic.

They are all capable of that. We know too little, for sure, IMHO.

In one of the news articles today it talked about how identifing this new strain, will enable the industry to develop the appropriate vaccination. This strain originated in China, the Chinese labs are developing the sequences and thus able to control the actual vaccination rights. In a very non polictal question, is the failure to release the completed sequences to the world based on a financial decision? It sure smells that way to me, but hey what do I know.

This is the link to my previous posts iin July on how new strains that are continuing to appear in southern China may pose a serious risk, and how they had become airborne in some instances on this thread, the top few posts, which can be summarized by this one:

anon_22 – at 11:34 To summarize, we are seeing:

1) frequent reassortment creating new strains

2) these new strains show increasing virulence in mammals

3) possible shift towards airborne transmission

EastTN – at 17:10

In one of the news articles today it talked about how identifing this new strain, will enable the industry to develop the appropriate vaccination. This strain originated in China, the Chinese labs are developing the sequences and thus able to control the actual vaccination rights. In a very non polictal question, is the failure to release the completed sequences to the world based on a financial decision? It sure smells that way to me, but hey what do I know.

Well, let’s say its a country that err on the side of non-disclosure as a default position, and that includes non-disclosure of reasons for non-disclosure, so it really is hard to tell.

Like I said before, there are places on this planet where train timetables or even the weather might be considered national secrets.

Referring to my 17:29 post, the 2nd and 3rd points are the reasons for my 16:58 and 17:03 comments.

ie it would be useful to know whether this new strain is following the same pattern of increasing virulence to mammals, and if so to what degree, and whether it is more frequently isolated from tracheal than cloacal samples.

bump

anon_22: Thank you for your summaries. Is there any way to know if the new strain emerged through reassortment, mutation or recombination? If we could infer which one, would one or the other have any implication for the ease of the new strain changing yet again to become pandemic? Sorry if this is a silly or too-basic question.

anon_22 – at 16:26

“No, it is a new strain, which very quickly became dominant.”

Interesting discussion, but I’m still having difficulty with how this is a new strain. Unless others have information not publically available, we only have 2 of the 8 gene segments from this latest Fujian-like virus to analyze. In looking at those two, there is very little difference from the older Clad 2, Subclad 3 Fujian H5N1. Yes there are some mutations, but nothing of much significance, and this virus remains very avian in nature. It doesn’t have some of the more disconcerning mutations of the Qinghai strain that has spread from Northern China across Asia and Europe.

Does someone have an analysis of the other six gene segments that they could share so that we have some solid information as to how this virus has so radically changed into a new strain?

Mamabird – at 20:16: I’m still having difficulty with how this is a new strain. Unless others have information not publically available, we only have 2 of the 8 gene segments from this latest Fujian-like virus to analyze. In looking at those two, there is very little difference from the older Clad 2, Subclad 3 Fujian H5N1. Yes there are some mutations, but nothing of much significance, and this virus remains very avian in nature. It doesn’t have some of the more disconcerning mutations of the Qinghai strain that has spread from Northern China across Asia and Europe.

What she said.

I find myself coming down on China’s side in this debate (that’s new).

Why is this change (recombination?) any different than the other changes that created new sub-clades. Are all new sub-clades now to be considered “new” strains? What am I missing here?

Mamabird – at 20:16

Interesting discussion, but I’m still having difficulty with how this is a new strain.

I wasn’t going to post the phylogenetic tree, but I guess I will now. :-)

Well, a picture is better than a thousand words. I hope you can read that. I wanted it to be on the same page here so you refer to it as you read posts. The last group on that chart, the whole of that group is very distinct from the other clades.

Here is the detailed one, of the HA gene, and it will open in a new window

anon_22 – at 20:50

Thanks a bunch anon_22 for that new information on HA evolution. I appreciate you going to so much trouble.

So, even though the HA of the latest isolates have only a few mutations diffent than the older Fujian viruse, it shows up as a new branch (strain) on the phylogenetic tree. Do we also have the phylogenetic tree for the PB2 gene? I would expect not much change in it. Also we do we have trees for the more unstable segments like the NA?

I mean this is helpful, but I’m puzzeled how this is a completely different strain when the HA cleavage site of this virus clad hasn’t changed to any degree, nor has PB2, as would be expected. I would further expect, not having seen the sequences, that the amino acid deletions in N1 and NS1 would also not have changed from the older variety.

In other words, this virus is not becoming more human-like as has the other clads. It is still just a very typical avian virus from what we can see from the evidence. High Path, of course, but a bird flu predominately that has escaped the ill formed Chinese vaccines. Certainly makes a case for culling, doesn’t it?

Here’s another chart, with bigger letters, courtesy of WHO. It’s from August, though.

(scroll down 3 pages) http://tinyurl.com/ykb7mj

Is the “new” Fujian strain not just the Fujian clade 2/ sub-clade 3 part of this chart? Distinct, yes, but why is it now not considered to be just a sub-clade of the regular old Fujian clade?

Why are all the other distinct sub-clades on the chart (sub-clade 1, sub-clade 2) not also considered new strains? (Your new chart might explain some of this, but the print is too tiny on my screen to see).

Well, I guess the uncertainty may be centered around the word ‘new’. I use it in the context of it being previously uncharacterized, and forming a very distinctive subclade. This description is neutral as to how it is formed.

Maybe the best way to explain this is to go back to Pixie’s original question, why are we not calling it the newly dominant strain. That description would apply if you have a virus from an existing sublineage, which then overtakes the rest of the virus in terms of numbers so that all new strains belong to that sublineage. In that case, that whole group would still belong inside one of the existing groups.

In this instance, it is more than that. The first of this subclade isolated was the Dk/FJ/1734/05 which right from the start was distinct from all the other sublineages. After that all subsequent isolates are closer to this one than other isolates and together they form a distinct branch that didn’t exist before.

Well, I’m no virologist, so maybe you can discern the meaning from this description. I’m trying not to quote too many bits otherwise we will end up with the whole paper here! (just kidding)

“To better understand the increased prevalence of H5N1 in poultry and the emergence of human infection in China, 390 (30% of total new isolates) of those avian H5N1 influenza viruses isolated from July 2005 to June 2006 plus 16 viruses isolated from smuggled poultry and dead wild birds in Hong Kong in early 2006 were sequenced and analyzed together with sequences available from public databases. Phylogenetic analysis of the HA gene revealed that 266 of 390 (68%) of those recent H5N1 viruses from southern China formed a previously uncharacterized and distinct H5N1 sublineage (FJ-like) (Fig. 3 and 4A). Twentyeight viruses isolated in Guiyang from November 2005 to January 2006 formed a sublineage (GY2) that is the sister group to the FJ-like sublineage (Figs. 3 and 4A).Another three sublineages from Guangdong (GD/06, n = 6), Guiyang (GY1, n = 14), and Yunnan (YN2, n = 13) also were identified. A further 59 viruses grouped in the Mixed/VNM2 sublineage, and only a single virus (Gf/ST/1341/06) belonged to the QH-like sublineage currently circulating in Africa and Europe (Fig. 3 and 4A). The remaining viruses analyzed in this study belonged to previously reported sublineages from China and Southeast Asia, except two isolates from Hunan (Ck/HN/2246/06 and Ck/HN/2292/06), isolated in May 2006 that do not fall with any of these sublineages (Fig. 4A).”

but I’m puzzeled how this is a completely different strain when the HA cleavage site of this virus clad hasn’t changed to any degree,

Actiually it has,

“those viruses from the FJ-like sublineage have a Gln3Leu substitution at position −9 from the cleavage site (LRERRR-KR/G).”

In addition, the antigenic analysis also show distinctive patterns that correspond as a group.

OK, I should go soon. Can’t type, need sleep.

anon_22 – at 21:19

I see the distinction that is being drawn by the research paper, and it is certainly appealing. However, let me be more precise in my lack of understanding of strains. If you take Pixie’s link to the earlier phylogenetic tree there is listed under Clad 2, subclad 3 Fujian an isolate labeled “A/duck/Laos3295/2006″. If you compare its HA genetic sequence with that of the more recent “Guiyang” isolates above cited, the only difference in the entire HA genome is I236V and I269M.

That’s only 2 amino acid differences between these two viruses, and they are not in “significant” positions. So, if we are calling this a new strain, I’m OK with that I guess, but I’m not sure I see much of an issue with the 400 plus new isolates released by these scientists. I know this “Fujian-like” bug is now dominant in Asia, but so is Qinhai throughout EuroAsia, and it is a mean motor scooter.

Mamabird,

One more thing, as I said I’m no virologist, but I have an observation. When you say, Yes there are some mutations, but nothing of much significance, and this virus remains very avian in nature. It doesn’t have some of the more disconcerning mutations of the Qinghai strain that has spread from Northern China across Asia and Europe. it tells me that you may have some preconceptions as to what kind of changes are significant and what not.

I may be wrong but I suspect it may be a better idea to remove those ideas and look at the whole picture afresh every time, and let the data tell you what is significant. Otherwise, we will fail to pick up interesting things that stare us in the face. Particularly since flu virology is still very embryonic, and a lot of notions are not much more than conjectures.

I’m still not sure what is the functional importance of distinguishing whether this is called a new strain, a variant strain, a new subclade, a different sublineage etc. Maybe someone can enlighten me.

But the biggest significance of this strain is its replacement of other strains. ie not only did it appear, but all other sublineages that have co-existed for a few years start dying out altogether in different provinces. Its like something comes along and sweeps everything else off the table, leaving this one to stand, but in every single place that it goes. I guess that does make it different and important, even compared to the Qinghai strain.

But please feel free to correct my interpretation of what this paper is saying…

Thank you all for this very interesting discussion.

Qinghai was important for several reasons, the dying off of wild birds, a new mutation, rapid spread to a lot of places, etc.

This current one is a different type of event. It is a replacement of a multiple sublineage pattern with a new (I’m going to use this word again, in the context that the first isolate was only identified in March 2005) single strain that in a very short time completely changed the pattern.

The importance is in whether this indicates a degree of fitness that other strains had not exhibited before. And whether this fitness in birds will translate into fitness in humans. Remember we know very little (next to nothing) about the genetic markers of what constitutes fitness, so we can’t make those determinations by sequence analysis. But we can determine that by looking at the behavior of the virus. The whole of China is the laboratory, in a way, where we are observing how this virus behaves in birds and in humans.

Still on the topic of fitness, I just remembered this. Taubenberger said it is possible that some of these characteristics that we are talking about like fitness are not determined by single mutations, but a combination of mutations, probably even on different genes.

I sent him this paper (not that he needed me to send it, but I did anyway) and asked him what this indicates in terms of fitness, but he hasn’t responded yet. Maybe I’ll ask him again in a couple of days.

Do you think that the Chinese vaccines might have killed off the competition? This Fujian-like virus may be getting some help. Let nature take its course and these viruses may not change as rapidly as what we are now seeing. Afterall, with all the help we have been giving, most are moving toward M2 and NA antiviral resistance.

Mamabird – at 21:58 Do you think that the Chinese vaccines might have killed off the competition?

That is what it looks like at the moment, at least according to this paper.

This Fujian-like virus may be getting some help. Let nature take its course and these viruses may not change as rapidly as what we are now seeing. Afterall, with all the help we have been giving, most are moving toward M2 and NA antiviral resistance.

Well, this one is not moving towards M2 and NA inhibitor resistance.

The only thing that will surprise me is when we don’t have any more surprises.

Yes, thanks for the excellent discussion anon_22.

Well, assuming that China has been forthcoming with the true number of human cases it has seen since March, 2005, then the virus has not aquired the kind of fitness that would make it as ubiquitous in humans as it has become in chickens. So far. Now if somebody knows whether what makes for fitness in birds is in any way related to the same thing that makes for fitness in humans, we can all solve the whole ball of wax. (Anybody need a topic for a PhD thesis??).

I saw an interesting interview yesterday with Ray Kurzweil, and he postulated that if string theory and multiple universes are plausible, then maybe we are all just some junior high school experiment hatched by a kid in an alternate universe. I bet that’s kinda how China feels about being the “lab” where H5N1 works out its experiment.

New Recombinomics commentary: Commentary

H5N1 Fujian Cleavage Site Evolution Recombinomics Commentary

November 6, 2006

But Chen Hualan, director of China’s National Bird Flu Reference Laboratory, said they “lack scientific proof” and that her lab hasn’t found one strain to be more prevalent than the others.

“The so-called ‘Fujian-like virus’ is not a new variant of the virus,” Chen was quoted as saying by the China Daily newspaper.

“Gene sequence analysis of the virus shows that it shares high conformity with the H5N1 virus that was isolated in Hunan when bird flu broke out in early 2004,” said Chen, whose lab does isolation and gene sequence analysis on samples from every domestic bird flu outbreak.

The above comments highlight differing views between researchers in mainland China and Hong Kong on the evolution and significance of the Fujian strain of H5N1 in China. Some of this disagreement may be related to the definition of the Fujian strain. The first H5N1 isolated in Asia was from a goose in Guangdong in 1996. It had an HA cleavage site of QRERRRKKR. Subsequently, various stains of H5N1 have emerged and they can be grouped by changes in the HA cleavage site, which are associated with additional changes throughout all eight gene segments.

Last weeks PNAS paper added 404 HA sequences to the database, which allows for easy tracing of the HA cleavage site. The Fujian strain has two changes. The first change involved the loss of one K, producing a cleavage site of QRERRRK_R. This cleavage site was first reported in late 2003 in a duck in Taiwan that was being smuggled from Fujian province, A/duck/China/E319–2/03, as well as a duck in Hunan, A/Dk/HN/5806/2003. Thus, as noted above, the missing K was detected in 2003. Moreover, the missing K can also be found in a 1998 H7N1 isolate from a peregrine Falcon in the United Arab Emirates, A/peregrine falcon/U.A.E./188/234/98. The list of H5N1 isolates with the missing K can be seen here. In addition to southern China, isolates in Indonesia in 2004 and Vietnam in 2005 were also found.

However, in the spring of 2005, a duck that had the missing K and the Q→L change was also found. The list of isolates with both changes is found here. The motif with the two changes spread rapidly throughout southern China, and included wild bird isolates in Hong Kong as well as isolates from Laos and Malaysia. Moreover, all human isolates from China in 2005 and 2006 had this change as did additional 2006 human isolates described in a report by China’s Ministry Of Health.

These Fujian isolates have regions of identity with the Qinghai strain and highlight the evolution of H5N1 via recombination. The HA cleavage site with just the dropped K was found in Indonesia H5N1 which was on an Indonesian genetic background, which was also seen in the 3′ half of the cleavage site which was also detected on an H7 genetic background. Similarly, one of the Indonesian isolates also had a Qinghai cleavage site on an Indonesian background.

However, it is recombination in wild birds between Qinghai and Fujian sequences that is driving the emergence of the new strain in China. Fujian sequences have also been detected in a Qinghai isolate in Romania, further highlighting the evolution of H5N1 via recombination.

It’s likely that recombinations can change the status of M2 and NA inhibitor resistance at any time, seeing as how the changes aren’t due to random mutations anyway.

anon_22 – at 21:39

“…it tells me that you may have some preconceptions as to what kind of changes are significant and what not.”

No, I’m afraid that I’m not that smart. But Taubenberger and his fellow co-workers are. There is a large volume of research that shows genetic characteristics of avian viruses, and genetic characteristics of human viruses. As Mr. T has indicated, the 1918 H1N1 was a very avian virus, but over the years has mutated to adapt to its human hosts. So has H3N2.

All eleven proteins formed by the eight gene segments can be statistically analyzed to see which amino acid positions are predominately human, and which ones are predominately avian. If you see any avian viruses that have amino acid positions that are mutating toward the human characteristics, you may wish to take note. The Fujian-like viruses have made little progress toward taking on those more human characteristics. However, other clads have, and so have other avian viruses, H9N2 for example that is all through China’s fowl and infecting humans as well.

The Fujian-like viruses have made little progress toward taking on those more human characteristics.

I don’t think the Webster group is saying that it is making progress towards human characteristics at all.

Well, I defer to other people’s wisdom when it comes to the fine art of classification and phylogenetic analysis. The most I can do on that department is to explain what someone says. :-) But I do know something this is something that made me sit up the first time I read it. For what it’s worth.

OK, I really should go. Happy virus-gazing, everyone.

anon_22 – at 22:15

“I don’t think the Webster group is saying that it is making progress towards human characteristics at all.”

“ABSTRACT: The development of highly pathogenic avian H5N1 influenza viruses in poultry in Eurasia accompanied with the increase in human infection in 2006 suggests that the virus has not been effectively contained and that the pandemic threat persists. …Viruses from this sublineage gradually replaced those multiple regional distinct sublineages and caused recent human infection in China.”

Maybe I just read too much into the Abstract. In all fairness, we really need to see the full text of this research, and it would be lovely to have a peek at all eight gene segments of the viruses that they have studied as well. I don’t wish to put words into anyone’s paper.

Mamabird, I still don’t see how that statement in the abstract is referring to progress towards human characteristics? Is that what you are saying?

I read the whole thing and I don’t think I came across that inference. The major inferences are the failure of current control measures and the emergence of a dominant strain.

anon_22 – at 22:24

“Mamabird, I still don’t see how that statement in the abstract is referring to progress towards human characteristics? Is that what you are saying?”

Well, yes, I guess that is the way I took it, mistakenly, I suppose. I just don’t quite see how a researcher can use the word “pandemic” without implying that the virus is able to to not only jump the species barrier, but has mutated sufficiently to become efficient H2H. Again, I appreciate the discussion because I have to make a presentation tomorrow to attempt to place the news media’s comments about this research into some sort of context. I’m just at a loss as to how to do that, but you have certainly helped me get my mind right.

Have a great evening all. Check you later with I hope better news from Asia.

bump

anon_22 – at 21:34

“those viruses from the FJ-like sublineage have a Gln3Leu substitution at position −9 from the cleavage site (LRERRR-KR/G).”

I missed the above comment last night, but please note that “A/chicken/Guangdong/178/04″ also has the “QLRERRR_KR*GLF” signature, so I don’t really see this change as a new event. There are quite a number of isolates that have the Gln change from earlier years. Further, since it doesn’t add any additional multiple basic amino acids at the cleavage site, I’m not sure that this change has much significance, but I could be mistaken.

Also, did the researchers that authored this paper claim that all the new virus detections have these changes in the Fujian-like strain? I mean if some did and some did not, then do we really have a new single dominent strain? Or perhaps, the old Fujian strain is all that’s left in the region after the Chinese nuked all the other competing strains with their vaccines?

Also, did the researchers that authored this paper claim that all the new virus detections have these changes in the Fujian-like strain?

Yes, that’s why I quoted that sentence.

A few months back in the release the sequences actions someone mentioned that Webster et al, were hoarding sequences too. Webster implied it was for papers. The sequences now made public for the Fujian like strain, were they possibly in these group of sequences held back for publishing? The reason I ask, because it might explain the difference of opinions and the study examined a lot of sequences.

How long does it take for a new strain to characterize dominance? Is there a time reference for a new strain to emerge?

anon_22 – at 15:53

“In addition, all 5 of the recent human cases with samples available were from the new strain. Below is a map of the provinces of China which is useful for this purpose. …the human samples were from 1 each from Guangdong, Guangxi, Zhejiang, and 2 from Anhui. (Map not shown)”

Anon_22, I went back once again and looked at the human sequences cited above (except for Guangdong which I could not readily locate). All of these human isolates have the old Fujian cleavage site “LRERRR_KR*GLF”. So none of these have the “Gln3Leu substitution at position −9″. Plus, there are only a few insignificant mutations from the other, older Fujian isolates, none at the recptor binding site. Such mutations or changes are expected from a gene segment that is not highly conserved.

So, I’m still stumpted about this new strain. Again, it would peachy if Webster, et al would release the other six gene segments that they have obviously analyzed. Without more information, this is just not very exciting news, but who knows, maybe the polymerase genes have some surprises for us.

http://online.wsj.com/article/SB116292692200415797.html

Bird-Flu Rift Shows China’s Travails

Reported New Virus Strain Demonstrates Difficulties Of Harnessing Research

By NICHOLAS ZAMISKA

THE WALL STREET JOURNAL

November 8, 2006

HONG KONG — An unusually public dispute between the Chinese government and a group of bird-flu researchers underscores that China is still wrestling with efforts to bring infectious-disease research under a single, state-sponsored umbrella.

<snip>

Dr. Guan has conducted independent research on viruses such as the one that caused the 2002–03 outbreak of severe acute respiratory syndrome, or SARS, and now on avian flu, which has killed at least 152 people, mostly in Asia, since it re-emerged in late 2003. He has often published conclusions that clash with the government’s stance.

The latest confrontation began last week when Dr. Guan, with 13 other scientists from Hong Kong and Memphis, Tenn., published a paper that identified what they said was an emerging variant strain of Chinese bird flu.

<snip>

A few days later, Liu Jianchao, spokesman for China’s foreign ministry, denounced the paper. Two top Chinese government scientists, including Chen Hualan, the director of China’s National Avian Influenza Reference Laboratory, joined the paper’s critics in an article published Sunday by the official Xinhua news agency. Dr. Chen said the paper’s claims “lack scientific proof.” She added, “The so-called Fujian-like virus is not a new variant of the virus.”

The disagreement is largely about the difficulty of identifying a “new” strain of a virus, since all viruses, including bird flu, evolve constantly. In this case, it remains unclear whether the virus is any closer than it was before to spreading easily among people. That transition is what scientists and public-health experts agree could cause a bird-flu pandemic, possibly killing millions of people.

But underlying the dispute is the fact that Hong Kong scientists, including Dr. Guan, continue to conduct virus surveillance in southern China outside the official government apparatus.

Mamabird – at 16:40

I don’t think we have an answer to your question any time soon.

They are operating under shall we say less than perfect conditions, so I don’t know whether there are reasons for giving Webster el al the benefit of the doubt for not sharing sequences.

Just saying….

bump for comments/attention.

from my 09:08 post

A few days later, Liu Jianchao, spokesman for China’s foreign ministry, denounced the paper.

Since when do Foreign Ministries care about scientific publication?

For those who didn’t get that, the Foreign Ministry was responsible for supporting the election of M Chan for WHO DG…

bump