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WHO. Antigenic and genetic characteristics of H5N1 viruses and candidate vaccine viruses developed for potential use in human vaccines (Feb. 2009)
hmm, same deletion as that what happened in human H1N1 1995 ?
kalign aligns it to the same positions
I looked harder at other serotypes and found two low path H5N2 sequences, but didn't see H1N1 from 1995. H2 is missing an amino acid in this area, but H2 doesn't have much homology with H5 in this region.
China's National Avian Infleunza Reference Laboratory at Harbin have deposited two new gene sequences (HA and NS) for the clade 7 isolate, A/chicken/Shanxi/2/2006, from the 2006 outbreak in Shanxi. In addition to changes in several single nucleotide polymorphisms, the new HA sequence has the 3 BP deletion that is in two other clade 7 sequences from Hunan, A/chicken/Hunan/2246/2006 and A/chicken/Hunan/2292/2006. This deletion is also in 12 clade 2.2 sequences from Egypt, including human isolates from the 2006/2007 season as well as the 2007/2008. The sharing of the identical 3 BP deletion by isolates from two distinct H5N1 clades provides compelling evidence for acquisition via homologous recombination. Moreover, sequences with the 3 BP deletion, as well as other sequences from Egypt, including sequences from vaccine resistant isolates share additional polymorphisms with the Shanxi sequence.
The new interest in the Shanxi sequence by the National Labs at Harbin adds to the circumstantial evidence that most or all of the six confirmed cases not discussed in the recent WHO report on H5N1 vaccine targets are clade 7, which was also reported for the Jiangsu poultry outbreak in China at the end of the year.
Although the WHO report did not discuss clade 7 in China, the variation in clade 7 in Vietnam was discussed because of the low cross reactivity between 2008 clade 7 isolates. The reduced cross reactivity between clade 7 isolates from the same country and year signals rapid evolution of clade 7, and the limited cross reactivity with antisera directed against clade 1 or clade 2 increases concerns.
The concerns regarding the rapid evolution of clade 7 in Vietnam are increased by the failure of WHO to discuss the six confirmed cases in China, including the Beijing isolate. A/Beijing/1/2009, which was from a fatal infection that began just after the clade 7 outbreak in Jiangsu.
Moreover, the sharing of polymorphisms between vaccine resistant clade 7 in China, and vaccine resistant clade 2.2 in Egypt raises concerns that these polymorphisms are being exported from China via migratory birds, contributing to worldwide vaccine failure.
Release of the 2009 human H5N1 sequences in China, Vietnam, and Egypt would be useful.
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"The next major advancement in the health of American people will be determined by what the individual is willing to do for himself"-- John Knowles, Former President of the Rockefeller Foundation
Re: WHO. Antigenic and genetic characteristics of H5N1 viruses and candidate vaccine viruses developed for potential use in human vaccines (Feb. 2009)
rapid evolution of clade 7
Why would this clade evolve more rapidly than others? If it's evolutionary fitness, what are the specifics?
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"The next major advancement in the health of American people will be determined by what the individual is willing to do for himself"-- John Knowles, Former President of the Rockefeller Foundation
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maybe the "same" position as far as one can compare H5 and H1
> reinsertion of K134 revealed the requirement of a compatible neuraminidase
The above paper describes a deletion that led to current H1N1's. These current H1's match H5's in the region where the 3 BP deletion leads to an additional loss in H5. The deleted H5 is deleted relative to H5 or H1 (it actually matches H2, but H2 has little homology in the region where the H5 aa is deleted.
Rapid H5N1 Clade 7 Evolution in Vietnam Raises Concerns
Recombinomics Commentary 14:31
February 25, 2009
Antigenic diversity is also present within clade 7 and viruses such as A/chicken/Vietnam/NCDV-03/2008 show reduced reactivity with antisera to clade 7 reference strain A/chicken/Vietnam/NCDV-016/2008.
The above comments are from the latest WHO update on H5N1 vaccine targets and represents concerns of a rapidly evolving clade 7 in Vietnam. The basis for the concern can be seen in the antisera table, where the vaccine against 016 has a titer of 320, which drops to 40 for 03. This drop is also suggested in the phylogenetic tree at the end of the report because of the length of each clade 7 node. Thus, even though both 016 and 03 are on the same branch, the length of each branch is relatively long, representing multiple changes.
Moreover, there are even more difference between the clade 7 in Vietnam and the clade 7 in China, represented by Shanxi/2. However, Shanxi/2 was from 2006 and China has already reported a clade 7 outbreak at the end of 2008, which likely has additional changes. Moreover, the clade 7 outbreak in poultry was followed by a spike in human cases, including A/Beijing/1/2009, which was almost certainly due to clade 7. The last human case in Beijing was in 2003 and was also clade 7, and clade 7 is common in poultry in areas surrounding Beijing.
The WHO report is glaringly silent on clade 7 in China. The Jiangsu outbreak was in December and sequences were generated last year because the OIE report noted the similarity with Shanxi/2. However, the Jiangsu poultry sequences are not on the tree and the only two human sequences from China in 2009 were from an infection with clade 2.3.4 or clade 2.3.2. There is not representation or comment on the other six confirmed cases, five of which were prior to the clade 2.3.2 infection. Moreover, the Beijing case began in 2008 and the sequences were described in general terms in media reports in early 2009.
The lack of any recent clade 7 sequences from China is cause for concern, as is the rapid evolution of clade 7 in Vietnam. In Vietnam, clade 7, clade 2.3.4, and clade 1 are co-circulating, providing opportunities for co-infections which lead to reassortant and recombination. Similarly, in China clade 7, clade 2.3.4 and clade 2.3.2 are co-circulating, offer similar opportunities. In fact the clade 2.3.2 from wild birds in Hong Kong, as well as the outbreaks South Korea, Japan, and Russia is a reassortant with a clade 2.3.2 HA and clade 2.3.4 in the other seven gene segments. Recombination between the clades and sub-clades leads to rapid evolution and vaccine resistance.
Thus, in addition to limited or no cross reactivity between clade 1 or 2 with clade 7, the published data supports rapid clade 7 involvement within clade 7. Thus, the vaccine against a 2008 clade 7 isolates from Vietnam has poor cross reactivity with another 2008 clade 7 isolate from Vietnam.
This rapid evolution of clade 7 in Vietnam, coupled with the absence of data on the current clade 7 circulating in China increase pandemic concerns.
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"The next major advancement in the health of American people will be determined by what the individual is willing to do for himself"-- John Knowles, Former President of the Rockefeller Foundation
Re: WHO. Antigenic and genetic characteristics of H5N1 viruses and candidate vaccine viruses developed for potential use in human vaccines (Feb. 2009)
Why would some areas, like China and Vietnam, have multiple circulating clades, while other areas have fewer or even only one circulating clade?
Is there any comparison to the human influenza norm, ie., one strain, with the cause of exceptions (like the current 2 As) being significant prior recent immunity (to H1N1) when a new strain (H3N2) attempts dominance?
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"The next major advancement in the health of American people will be determined by what the individual is willing to do for himself"-- John Knowles, Former President of the Rockefeller Foundation
Re: WHO. Antigenic and genetic characteristics of H5N1 viruses and candidate vaccine viruses developed for potential use in human vaccines (Feb. 2009)
why are there more species of birds,beetles,... in some areas ?
All sorts of reasons. Airtravel is one of them. Weather,habitats,
Also several strains within H1N1,H3N3, 5-10 per season in USA
so 5-10 independent introductions.
Rarely both H1 and H3 cause widespread infections, usually
there are "H1-seasons" and "H3-seasons". Last season was an exception,
2006/7 also. So presumably they infer some protection/immunity
to each other during the same season
Last edited by gsgs; February 26, 2009, 06:18 AM.
Reason: typo
Why would some areas, like China and Vietnam, have multiple circulating clades, while other areas have fewer or even only one circulating clade?
Is there any comparison to the human influenza norm, ie., one strain, with the cause of exceptions (like the current 2 As) being significant prior recent immunity (to H1N1) when a new strain (H3N2) attempts dominance?
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The seasonal flu examples are of two different serotypes, while all of the sub-clades and clades mentioned for Vietnam are of the same serotype (H5). Genetic exchanges between members of the same serotype are much more common, which is why most of the examples of recombination look like SNPs.
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