Rhiza Labs FluTracker Forum

Do you mean North and South America are equivalent as bird flu reservoirs?

no, but related.

like Asia and Australia
Europe and Africa

(I had lookd at the Argentinean tinamou)

_________________
no patents on genes, publish the GISAID sequences !

OK, sampling universe excludes mammalian hosts and is bound to avian hosts. Focus is avian flu.
Nevertheless, the H5N1 patway is markedly different from other avian flu he’ve seen thus far.
viewtopic.php?f=26&t=1734&start=250
Pattern suggests that the avian H5N1 subset of “flu-sphere” suffers some “interference”,
possibly linked to its epizoonotic capabilities to infect humans (+ swine?).

It used to be common sense that most avian influenza genes do not cross the “species barrier”.
Could H5N1 show a “genetic tunneling” (ie genes or gene acquisitions crossing
“forbidden” avian/mammal “species barrier”).

Otherwise, how could H5N1 acquire specific human infetivity traits?
I feel the “interference” pattern on H5N1 cloud distribution coud reflect that.
As a reference, I also quote a 2004 Niman’s Commentary on the specific subject:

http://www.recombinomics.com/News/0820043/swine_human_signatures.html

when we talk about H5N1 here, then we mean the H5 (HA) of H5N1 only.
The other segments (6 not so much) were/are frequently changed by reassortments
with other strains.

This H5-HA first appeared in goose/Guangdong/1996.
We don't know where it came from.
But it is particularly distant in the cloud pictures from wild bird H5s.
That may indicate prolonged replication in poultry (for years,decades)

Related H5s were found in Italian chickens in 1997.

H5 can be low-pathogenic and high-pathogenic, there are several
examples where it mutated in poultry flocks from LP to HP.

Usually in wild birds it is LP, while the 1996ff H5N1 is HP.
I haven't heard, that it can mutate back from HP to LP.

_________________
no patents on genes, publish the GISAID sequences !

I add some links to papers which are interesting in this context
and which I want to read...

http://www.ncbi.nlm.nih.gov/pmc/article ... 5-0531.pdf
http://mbe.oxfordjournals.org/cgi/conte ... 23/12/2336
http://jvi.asm.org/cgi/content/full/82/7/3769
http://pubs.acs.org/doi/abs/10.1021/ci9001662
http://vir.sgmjournals.org/cgi/content/full/85/8/2327
(thanks to MH for sending some of these)


the idea of "stasis" in the evolution of protein-sequences of avian
influenza was mentioned before.
It was argued that the virus were "near optimal" and thus
there was not much need to further evolve.
It is never near optimal in humans, though.

Another theory is IMO, that a virus-segment is protein-stable near
the index in some avian species (mallards ?) or transmission modes (water ?)
and is quite well preserved there, while it
moves away from the index in other species, i.e. poultry
but then usually dies out.

I find it amazing that despite all this research I never found these
examples of low-amino-acid - vs. many nucleotide- differences
mentioned. And on different continents with separate evolution.
Maybe researchers either consider amino-acid or nucleotide
differences but not both simultaneously.

_________________
no patents on genes, publish the GISAID sequences !

I’ve been thinking about this avian flu amino acid pattern preservation
under a substantially different nucleotide encoding.

I also see that under evolutionary pressure such a host change,
the existence of these two “index like” genome classes on avian reservoir
can be quite a strategic advantage.

Different nucleotide encoding of the same amino acids, albeit synonymous,
widens the range of different potential acquisitions.
* * *

The recent interest on low reactor strains issue reminds me
a related synonym nucleotide encoding issue.

One of the first low reactor - A/Austria/501483/2009 - was found to display
more than 100 synonym changes.
Moreover, nucleotide correlation to amino acid apparently used set of quite non-standard codon rules.
As I remind, this and other sequences were further revised. I didn't check that further.

An abundance of synonym changes is probably atypical for a mammalian flu,
but is not exceptional for an avian flu, as we already verified.
During the off-equilibrium pandemic flu evolution, do you expect
a similar pattern eventually to show up on pandemic H1N1 sequences?

In our main-examples the viruses evolve separately on different continents.
But we have sub-clouds with fewer nucleotide-differences and same
protein sequence also on one continent.
But I don't think this is because of an evolutionary advantage. (is it really ?)
It just happened, flu evolves.


no, I don't expect this in human flu. It didn't happen before, not so many nucleotide-differences
with zero amino-acid-differences.

_________________
no patents on genes, publish the GISAID sequences !

in several inner segments of influenza A we typically only see limited (~10)
amino-acid changes in wild avian flu so that these segments are close to the calculated
"index"-protein-sequence here:
http://www.zonegrippeaviaire.com/showpost.php?p=51546
Synonymous changes are not affected and do occur at normal rates.

No such restriction is observed in mammalean flu,
which accumulates ~2.5*10^-3 nucleotide changes
and ~4*10^-4 amino-acid changes per position per year.
(6 nucleotide changes and 0.8 amino-acid changes in PB2 per year in humans)

Poultry and swine are in the middle between mallards and humans
wrt. protein-sequence-diversity = distance to the index :
mallards-wild birds-poultry-swine-humans

These index-like protein sequences occur independently
on different genetical backgrounds. So do the exactly same
(or more often: almost identical) protein sequences appears in
North-American and Eurasian lineages where usually we do see
separate evolution.
But while the protein sequences are similar, there are many synonymous
nucleotide differences, signalling a distant common ancestor.
So, A/blue winged teal/Ohio/926/2002(H3N8)
and A/mallard/Netherlands/2/2005(H4N2) have
0 amino-acid differences (identical to the PB2-index)
but have 343 nucleotide differences. There are other such examples and some
viruses only have 0-3 differences to the index in all inner segments.

This phenomenon can be visualized by plotting protein-differences
vs. nucleotide-differences of pairs of avian flu segments:
http://magictour.free.fr/panflu/seppp12.JPG
The "clouds" approach the y-axis high above zero.
The same picture for humans shows proportional acquisition of protein-
and nucleotide-difference:
http://magictour.free.fr/panflu/sepph3.GIF


discussion here: viewtopic.php?f=26&t=1734

_________________
no patents on genes, publish the GISAID sequences !

I have a first picture for protein-mutations , segment 3

http://magictour.free.fr/panflu/SEPP3B34.JPG
(green = poultry)

hmm, protein and nucleotide mutations in one line would be nice,
but it makes the lines very long


right bars are
substrain (1 or 2 for NA, 1 (so far) only for rest)
continent 1=NA,2=EU,3=As,4=rest
species 1=chicken,2=turkey,3=mallard,....,19=stork
year


spot how the black vertical marker lines are assigned to the continents
(some few overlaps ?)
poultry seems to have more mutations more black pixels


I could do the horizontal sorting as in the 3 here:
http://www.setbb.com/fluwiki2/viewtopic ... m=fluwiki2

but it's tedious...


2783 avian PAs
(horizontal green lines are from poultry , orange from wild birds)
The grouping(sorting) is not so good
On the left the virus-names as one pixel per letter

viruses are horizontal lines, as usual. Mutation positions are vertical lines.
Protein-sequences as this are 3 times shorter than nucleotide-sequences.
Positions with zero or only one viruses having that mutation are omitted,
so the lines are only ~500 pixels long instead of 720.

it's a first version, I should add descriptions


in the second bar on the right you see a pixel in each line depending on the continent.
Most left is NA,...etc
It starts with one virus from NA, then one from Asia, then lots from NA, one from Asia ...

_________________
no patents on genes, publish the GISAID sequences !

==============================================

2360 avian segment1s by species

1 average nucleotide-differences to other sequences in the list
2 average protein-differences to other sequences in the list
3 ratio 2/1
4 average AT-score (proportion of A,T nucleotides)
5 number of sequences from that species
6 name of species

segment 1
   1    2    3     4    5    6 
-----------------------------------
 1138  121  106  5487   14 widgeon
 1148  129  112  5483   51 shoveler
 1278  146  114  5486    3 tern
 1111  128  115  5472   73 pintail
 1136  131  115  5486  113 teal
 1134  133  117  5487  455 mallard
 1131  141  125  5487  146 turnstone
 1120  153  136  5508   31 stork
 1218  165  136  5513   19 shorebird
 1247  173  139  5525   47 gull
 1182  170  144  5517  327 Dk
 1252  185  148  5504  117 /Tk/
 1183  175  148  5508  141 
 1218  188  154  5491   35 fowl
 1276  199  156  5505    6 ostrich
 1159  185  160  5514   56 Gs
 1161  192  165  5539   33 swan
 1236  206  167  5542   33 /Qa
 1222  213  175  5548   10 pheasant
 1224  223  182  5530  623 Ck/
 1447  286  197  5693   10 stint
 1290  265  205  5574    5 avian

==============================================

segment 2
   1    2    3     4    5    6 
--------------------------------
 858  115  134  5680  519 mallard
 859  117  136  5688  131 teal
 849  115  136  5693   72 pintail
 834  118  141  5691   68 shoveler
 865  124  144  5667  186 turnstone
 892  130  146  5660   19 shorebird
 886  130  147  5687   14 widgeon
 957  142  149  5626    5 tern
 961  146  152  5688   50 gull
 884  138  157  5736   32 stork
 919  146  159  5671  155 rest
 926  148  160  5673  397 Dk
1115  182  163  5686   12 stint
 922  152  165  5700   36 swan
 913  152  167  5676   64 Gs
 901  152  169  5655   35 fowl
 930  159  171  5651  131 /Tk/
 944  174  184  5660   32 /Qa
 945  176  186  5630    7 ostrich
 952  186  195  5682  639 Ck/
 926  187  202  5664   13 pheasant
 991  245  247  5699    8 avian

==============================================

segment 3
   1    2    3     4    5    6 
--------------------------------------
 944  179  190  5579   68 pintail
 987  188  190  5597  174 turnstone
1011  195  192  5606   23 shorebird
 949  187  197  5568   14 widgeon
 958  191  199  5583  144 teal
 955  190  199  5585  532 mallard
 975  197  202  5572   62 shoveler
 956  193  202  5600   52 gull
 940  210  223  5612    5 tern
 916  217  236  5586  140 /Tk/
 862  209  242  5586    9 ostrich
 919  223  242  5603  167 
 891  222  249  5594  455 Dk
 994  250  251  5622   41 fowl
 835  218  261  5563   30 stork
 931  244  262  5595   13 pheasant
 883  232  263  5608   99 Gs
 863  229  265  5623   39 swan
 986  266  270  5652   66 avian
 947  257  271  5588   44 /Qa
 953  273  287  5613  708 Ck/
1144  355  310  5735   11 stint

 1134  133  117  5487  455 mallard
 1182  170  144  5517  327 Dk
 1224  223  182  5530  623 Ck/

  858  115  134  5680  519 mallard
  926  148  160  5673  397 Dk
  952  186  195  5682  639 Ck/

  955  190  199  5585  532 mallard
  891  222  249  5594  455 Dk
  953  273  287  5613  708 Ck/

flu acquires more amino-acid mutations in poultry than
in wild birds. It also increases the AT-score which is
higher in human viruses than in avian ones.
Wild bird amino-acid (=protein-) sequences are closer
to the avian index.
In poultry it mutates away from the index.
We saw this in H5N1 and in H9N2.
We have prolonged evolution of avian flu over decades
in H9N2 and I assume we also had it in H5N1.

There were several examples how low pathogenic H5 or H7
became high pathogenic after some months of evolution in poultry stocks.

So, it somehow "adapts" to humans by evolution in poultry.
You may see poultry as a "mixing" vessel like swine.
Poultry viruses like H9N2 or H5N1 should be more likely to
cross to humans.
The Dutch outbreak in 2003 was however caused by a
wild-bird-like virus crossing over to poultry.
These viruses should be less likely to persist and evolve for years.

Poultry viruses and mammalean viruses usually die after decades,centuries
when new viruses from the wild-bird reservoir are introduced
on rare occasions and causing pandemics/panzootics and replace
previousy existing strains.
Evolution in the wild-bird reservoir seems to be superior despite
the limited variation close to the bird-index.
The reason could be increased reassortment i.e. with
different HAs,NAs,NSs

_________________
no patents on genes, publish the GISAID sequences !