H5N1 and H1N1(2009) reassortment – are we quacking up the wrong tree?

[JJackson]

In the text box below I was thinking about the dangers of an H5N1 reassortment with pandemic flu. This was considered as occurring in a human but it is worrying to find that there are now sequences for H1N1(2009) in Turkeys at both GISAID & Genebank. I had thought that this flu would be common in mammals but was not expecting it to grow well in birds. While it was in humans ? and to a lesser extent pigs ? I was quietly confident there were so few human cases of H5N1 that reassortment may not be too much of a problem. If the pandemic strain drives out the seasonal strains then even if it does occur it has only one strain to mix with. End of good news.
The situation changes radically if the pandemic strain is happy in birds. WhileTurkeys are not a problem ? for the same reason we aren?t namely H5N1 kills us both ? ducks, or any other species which can get a dual infection with mild symptoms and spread it, are a very great problem. Added to which ducks can carry the complete flu toolkit - so the range of potential recombinations and reassortments is enormous. If H1N1(2009) start to show up regularly in aquatic fowl my level of concern will rise rapidly.
Anyone have some nice reassuring words as to why I should not be worrying?

Extending the hypothetical a little further - and wondering even further off topic ? let?s consider the implications for speculation around the merger with HP H5N1. Mercifully there has not been a reassortment or recombination event between H5N1 and any other flu ? at least not one that was viable. How might the current pandemic change the status quo? Initially it may seem to be a bad thing in that in pandemic years there are likely to be more humans with flu and ? assuming this has no bearing on the frequency of human H5N1 infections ? an increased risk of dual infection. Once the number of us that are immune, by vaccine or infection, has increased this effect will fade and ? again assuming H1N1(2009) displaces some or all of the seasonal strains ? we should have a reduced risk of a viable H5 pandemic. While we have no idea how many of the billions of permutations between H5N1 and other serotypes would create viable high path forms we can say that if you reduce the available permutations by limiting the strains to one and making that one very homogeneous then the chances of any of those ?bad? permutations occurring are greatly reduced.

Taken from this thread

 

[gsgs]

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

viruses distant from the bird-index do not happily spread in wild birds.
Poultry is another issue

 

[AlaskaDenise]

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

viruses distant from the bird-index do not happily spread in wild birds.
Poultry is another issue

However, there is nothing preventing a virus distant from the bird-index from acquiring genes from either poultry or wild birds then happily spreading the new-and-improved version amaong mammals, especially when it has demonstrated that it can merrily hop to turkeys if it so pleases.

JJ:

WHile many share your concerns, perhaps the best use of resources is to propose strategies to prevent such a reassortment. FluTrackers & other Blogosphere participants could be that incubator. For instance - do as some SE Asian countries are starting to do - vaccinate against H5N1, or at least among poultry handlers & families with backyard flocks. That would be a worthwhile investment for developed countries. Just imagine where we'd all be, if swine handlers had been vaccinated against influenza strains endemic in swine.

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[gsgs]

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

no spread of mammalean viruses in turkeys

except some triple-reassortants in NA

but no spread to wild birds

except ominous South Dakota ducks

 

[JJackson]

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

I hope you are right gsgs but it is early days for this strain and there have not been many wild bird sequences since the pandemic strain become widely dispersed.

 

[Gert van der Hoek]

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

Good old seasonal H1N1 can be found everywhere, including in wild birds.

Is there any reason the new H1N1 could not inch along the same path?

Edit:

From website Oregon Veterinary Medical Association:

Pet Birds
Pet birds can also be susceptible to H1N1. Testing is recommended if the bird and owner both develop an influenza-like illness compatible with H1N1.

http://oregonvma.org/news/h1n1

It would be nice to know why they say this?


Edit # 2 From American Veterinary Medical Association:

Q: The 2009 H1N1 virus has infected poultry. What about my pet bird? Can it be infected?

A:We know it can infect poultry, but we don't know if it can affect other birds (including pet birds).

http://www.avma.org/public_health/influenza/new_virus/new_flu_virus_faq_pet_owners.asp

So the answer seems to be: we don't know.

 

[JJackson]

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

The pandemic form of H1N1 is far removed from seasonal H1N1 and the HA is in fact more similar to H1 in H1N1(1918). I would have to look at the sequence data but as far as I know seasonal H1N1 does not infect birds but there are also separate avian H1N1 lineages. Gs may have looked at this as he looks at more sequences than I.

 

[Gert van der Hoek]

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

Virologie. 1980 Jul-Sep;31(3):243.

Isolation of influenza virus A/USSR 90/77 (H1N1) from wild birds.

Edit:

Abstract:

Eleven influenzavirus strains, of the antigenic subtype A/USSR 90/77 (H1N1) were isolated from 6 species of wild birds (gray heron, Ardea cinera; great cormorant, Phalacrocorax carbo; arctic loon, Garia arctica; squacco heron, Ardeola valloides; gargany, Anas querquedula and glossy ibis, Plegadis falcinellus).

5 of the birds had high titres of antibodies to influenza antigen A/USSR 3/75 (H1N1).

http://www.cababstractsplus.org/abstracts/Abstract.aspx?AcNo=19812263837

Edit # 2


Virology. 2010 Jan 5;396(1):76-84. Epub 2009 Nov 6.

First isolation of an H1N1 avian influenza virus from wild terrestrial non-migratory birds in Argentina.

Alvarez P, Mattiello R, Rivailler P, Pereda A, Davis CT, Boado L, D'Ambrosio E, Aguirre S, Espinosa C, La Torre J, Donis R, Mattion N.

Centro de Virología Animal, Instituto de Ciencia y Tecnología Dr. César Milstein, CONICET, Saladillo 2468, (1440) Buenos Aires, Argentina.

A type A avian influenza (AI) virus was isolated from dead or severely ill red-winged tinamous (Rhynchotus rufescens) found in a hunting ground in April 2008 in Argentina.

The subtype of A/red-winged tinamou/Argentina/MP1/2008 was determined as H1N1 by sequence analysis.

The cleavage site of the viral hemagglutinin corresponded to a low pathogenic influenza virus, although the clinical presentation and pathological studies suggest that the virus was pathogenic for red-winged tinamous.

Phylogenetic analysis of the viral genome suggested that while the hemagglutinin and neuraminidase genes were related to AIV from North America, the internal genes were most closely related to other South American isolates.

These findings support the postulated South American phylogenetic lineage for AIV PB2, PB1, PA, M and NS genes, and suggest that the evolutionary pathways of HA and NA genes involve exchanges between the Northern and Southern hemispheres.

http://www.ncbi.nlm.nih.gov/pubmed/...med_ResultsPanel.Pubmed_RVDocSum&ordinalpos=1

http://www.flutrackers.com/forum/showthread.php?t=133019


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[Gert van der Hoek]

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

(seasonal) H1N1 & H5N1 & H3N1 party going on in China?

H5N1 reluctant to court with H1N1?


Bing Du Xue Bao. 2009 Mar;25(2):131-6.

[Phylogenetic analysis of the neuraminidase genes of subtype N1 viruses in domestic ducks in eastern China]

[Article in Chinese]

Qiu BF, Liu WJ, Tang YH, Peng DX, Liu XF.

Key Laboratory of Animal Infectious Diseases of Ministry of Agriculture, Yangzhou University, Yangzhou, China. baofengqiu2008@yahoo.cn

To examine the phylogenetic information regarding the gene pool of AIV in domestic ducks in eastern China, the NA genes of twenty-six viruses isolated during 2002-2006, including two H1N1 strains, ten H3N1 strains and fourteen HSN1 strains, which reflected the predominant N1 subtype viruses were subjected to phylogenetic analysis.

The results indicated that AIVs of N1 subtype circulating in domestic ducks in eastern China were undergoing a gradual evolution.

Analysis of the deduced amino acid sequences revealed that NAs from all isolated H5N1 viruses had a 20-aa deletion in the stalk region (residues 49-68), whereas no deletion was seen in the NAs from other HA subtype viruses.

The viruses of H3N1 and H1N1 might have a propensity for reassortment of NA genes, whereas no direct evidence of reassortment of NA gene was obtained in H5N1 viruses.

PMID: 19678568 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/...ed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=19

 

[AlaskaDenise]

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

............I would have to look at the sequence data but as far as I know seasonal H1N1 does not infect birds but there are also separate avian H1N1 lineages. ........

Looking at the HA for avian/H1N1 for ALL years, there are 95 samples with some minor diversity, most of which are wild birds.

HOWEVER, when I added in human H1N1/HA from 12/1/08 to 12/31/08, and aligned them with the bird/H1N1 sequences......they have almost entirely different genes.

BTW - all avian H1N1 sequences have 225G.

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[JJackson]

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

Re: H5N1 and H1N1(2009) reassortment – are we quacking up the wrong tree?

Dutchy and AD thank you both for finding the data.

As in all things flu, if it is possible it probably will happen but it is a numbers game. We will have to wait a while to see how frequently it happens. If it transpires that the pandemic strain can consistently cause infection in the same species as H5N1,– be it bird or mammal,– then it is a concern. Ducks are the worst just because they are the reservoir for almost every known serotype and if the problem has not been that reassortments are rare, but has been that they just have not had the right palette from which to create a fit strain then ducks are the place to redress that problem.

 

[gsgs]

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

AFAIK, the only bird at genbank that ever caught a human virus
is one duck from Nanchang

the paper from 1980 maybe just found birds with ancestors of 1918 spainflu,
although that would also be very interesting.
Unfortunately these sequences from Russia are not available

getting a virus, like the turkeys , and spreading,mutating,reassorting
it as commonly seen in wild birds is another thing.
Even poultry viruses usually don't go to wild ducks.
H5N1 could be an exception. The mode of spreading is different
in the wild --> much reassortment

 

[AlaskaDenise]

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

Re: H5N1 and H1N1(2009) reassortment – are we quacking up the wrong tree?

.... If it transpires that the pandemic strain can consistently cause infection in the same species as H5N1 – be it bird or mammal – then it is a concern. Ducks are the worst just because they are the reservoir for almost every known serotype and if the problem has not been that reassortments are rare, but has been that they just have not had the right palette from which to create a fit strain then ducks are the place to redress that problem.

I just looked at 1976/H1N1 in humans, swine, and avian - all different again.

If in fact, influenza rarely passes directly from birds to humans, we're back to what some experts have said for at least 15 years now - monitor swine.
If swine can be isolated from both birds and humans, and also tested, then that may be the way to prevent more avian-sourced HP mutations. Of course, that assumes scientists can identify those factors, which they all admit they cannot do with 100% certainty.

Maybe the swine industry can borrow a concept from the poultry industry - use of sentinel chickens - except the swine industry can use sentinel ferrets!

.

 

[Gert van der Hoek]

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

This could be a comfort:


Homologous Recombination Is Very Rare or Absent in Human Influenza A Virus

Maciej F. Boni,1,2* Yang Zhou,3 Jeffery K. Taubenberger,4 and Edward C. Holmes3,5

ABSTRACT

To determine the extent of homologous recombination in human influenza A virus, we assembled a data set of 13,852 sequences representing all eight segments and both major circulating subtypes, H3N2 and H1N1. Using an exhaustive search and a nonparametric test for mosaic structure, we identified 315 sequences (2%) in five different RNA segments that, after a multiple-comparison correction, had statistically significant mosaic signals compatible with homologous recombination.

Of these, only two contained recombinant regions of sufficient length (>100 nucleotides [nt]) that the occurrence of homologous recombination could be verified using phylogenetic methods, with the rest involving very short sequence regions (15 to 30 nt).

Although this secondary analysis revealed patterns of phylogenetic incongruence compatible with the action of recombination, neither candidate recombinant was strongly supported.

Given our inability to exclude the occurrence of mixed infection and template switching during amplification, laboratory artifacts provide an alternative and likely explanation for the occurrence of phylogenetic incongruence in these two cases.

We therefore conclude that, if it occurs at all, homologous recombination plays only a very minor role in the evolution of human influenza A virus.

http://jvi.asm.org/cgi/content/full/82/10/4807?view=long&pmid=18353939-plane.com/

thanks to Revere

 

[Hogweed]

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

[
We therefore conclude that, if it occurs at all, homologous recombination plays only a very minor role in the evolution of human influenza A virus.

http://jvi.asm.org/cgi/content/full/82/10/4807?view=long&pmid=18353939-plane.com/

thanks to Revere

If I understand correctly Niman's answer to this is that they were looking for long recombinant chains when very short sequences including SNPs are the norm.

From the paper there were 313 sequences (2% of total) which "had statistically significant mosaic signals compatible with homologous recombination. " but were too short for them to analyse using "phylogenetic methods"

Also from the paper:

Finally, although there were 315 sequences in the data analyzed here that carried a strong mosaic signal as identified by 3SEQ, it was impossible to verify the vast majority of these as recombinants, since the putative recombinant regions were too short to infer a credible phylogenetic history. It is therefore possible that homologous recombination, should it occur in influenza A virus, more commonly involves the transfer of very short sections of RNA, a process that would be undetectable by the majority of other methods devised to detect recombination. If homologous recombination of short segments is determined to be a relevant process in influenza A virus evolution, the basis of our more frequent observation of mosaicism in A/H3N2 viruses compared to A/H1N1 viruses will need to be investigated further.

 

[SusanC]

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

Some interesting findings that may be relevant to this discussion:

The Evolutionary Genetics and Emergence of Avian Influenza Viruses in Wild Birds
Vivien G. Dugan,1 Rubing Chen,2 David J. Spiro,3 Naomi Sengamalay,3 Jennifer Zaborsky,3 Elodie Ghedin,4 Jacqueline Nolting,5 David E. Swayne,6 Jonathan A. Runstadler,7 George M. Happ,7 Dennis A. Senne,8 Ruixue Wang,1 Richard D. Slemons,5 Edward C. Holmes,2,9 and Jeffery K. Taubenberger1*

Together, these global genomic data provide new insight into the different evolutionary dynamics exhibited by influenza A viruses in their natural wild bird hosts and in those viruses stably adapted to novel species (e.g., domestic gallinaceous poultry, horses, swine, and humans). Based on these analyses, we hypothesize that AIV in wild birds exists as a large pool of functionally equivalent, and so often inter-changeable, gene segments that form transient genome constellations, without the strong selective pressure to be maintained as linked genomes. Rather than favoring successive changes in single subtypes, geographic and ecologic partitioning within birds, particularly within the different flyways, coupled with complex patterns of herd immunity, has resulted in an intricate fitness landscape comprising multiple fitness peaks of HA, NA and NS alleles, interspersed by valleys of low fitness which prevent the generation of intermediate forms (Figure 4aFigure 4).

In contrast, stable host switching involves the acquisition of a number of (as yet) poorly characterized mutations [24],[33],[52],[53] that serve to separate an individual, clonally derived influenza virus strain from the large wild bird AIV gene pool. Because adaptation to a new host likely limits the ability of these viruses to return to the wild bird AIV gene pool [24],[54], these emergent viruses must evolve as distinct eight-segment genome configurations within the new host. The ability of recent HP H5N1 AIV to cause spillover infections in wild birds is an unprecedented exception. Further, because humans represent a large and spatially mixed population, natural selection is able to act efficiently on individual subtypes [55]. Hence, a limited number of subtypes circulate within humans and evolve by antigenic drift to escape population immunity.

Notably, the recent Asian lineage HP H5N1 AIV strains are intermediate between these two contrasting influenza ecobiologies; a combination of large poultry populations allows natural selection to effectively drive rapid antigenic and genetic change within a single subtype [46],[56], while reassortment with the wild bird AIV gene pool facilitates the generation of new genome constellations [57]?[59].

Also check out this graphic - a picture tells a thousand words The fitness landscapes of avian influenza virus.

 

[sharon sanders]

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

How do they know this?

"The ability of recent HP H5N1 AIV to cause spillover infections in wild birds is an unprecedented exception."

It seems to me that the field tests to confirm this would be a huge undertaking. It seems to me that "spillover infections" are the rule in nature as we can see with the spread of A/H1N1 multiple species are being infected.

 

[SusanC]

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

How do they know this?

"The ability of recent HP H5N1 AIV to cause spillover infections in wild birds is an unprecedented exception."

It seems to me that the field tests to confirm this would be a huge undertaking.It seems to me that "spillover infections" are the rule in nature as we can see with the spread of A/H1N1 multiple species are being infected.

What they mean is that in general, flu viruses in wild birds exist as constellations of interchangeable genes (especially the internal genes) co-existing without the need to commit to a particular genotype, sort of like a 'RNA soup', whereas once a particular strain has adapted to other hosts (including, as they said gallinaceous birds such as turkey, chicken or quail, and mammals) it loses this ability and becomes committed as a particular subtype eg H5N1, H1N1 etc, and they do not tend to go back to wild birds (ie it's a one-way street) The chart at the last link (don't know how to post pics here, sorry) has a very good graphic that illustrates the concept.

H5N1 is somewhat of an exception because the finding of E627K, a mammalian adaptation, in wild birds is unprecedented. There are no other examples of a flu virus that has adapted to new species beyond wild birds, and then gone back to infect them! That we know of, at least. Exactly why that happens, is still something to be worked out.

 

[sharon sanders]

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

from August 2006 -

"Many factors have contributed to the problem there today according to Dr. Butcher: co-existence of chickens and humans, lack of implementation and enforcement of government regulations, many small flocks scattered in many geographical areas, and disposing of dead infected chickens in open pits which allows wild birds to become re-infected and thus start the cycle again. Also contributing to the problem is the fact that the poultry industry 'is not highly developed – not highly integrated.'"


http://www.flutrackers.com/forum/showthread.php?t=9457

 

[SusanC]

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

Re: H5N1 and H1N1(2009) reassortment ? are we quacking up the wrong tree?

from August 2006 -

"Many factors have contributed to the problem there today according to Dr. Butcher: co-existence of chickens and humans, lack of implementation and enforcement of government regulations, many small flocks scattered in many geographical areas, and disposing of dead infected chickens in open pits which allows wild birds to become re-infected and thus start the cycle again. Also contributing to the problem is the fact that the poultry industry 'is not highly developed ? not highly integrated.'"


http://www.flutrackers.com/forum/showthread.php?t=9457

Well, I'd say, while the close proximity of species is always a contributing factor to virus jumping across species barriers, that in itself cannot tell us which way the virus tends to jump - wild birds to chickens? Or vice versa? Or both ways?

The finding of E627K in wild birds is a different class of evidence than the kind cited by Gary Butcher, because this is a distinctly mammalian adaptation that is not seen in any other avian viruses, and therefore constitutes pretty strong if not solid evidence of H5N1 being able to cross BACK into wild birds. However, this is anomalous to the sum total of evidence on sampling of avian flu viruses in wild birds, from Dugan et al, suggesting that the behavior of H5N1 is likely to be the exception to the rule. Which means it's probably a good idea to not extrapolate information from H5N1 to other subtypes, since H5N1 does seem to be an unusual virus quite unlike the more 'everyday' ones like H1N1.

I just thought that this might be an important point to bear in mind, in our assessment of H1N1, since there is no evidence of H1N1 crossing back into wild birds since its emergence from them , even though obviously there are avian H1N1s in wild birds as well! (again this pic explains it well, if someone can help load it. Thanks!! http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2387073/figure/ppat-1000076-g004/