since when is there influenza in humans ?

[gsgs]

Re: since when is there influenza in humans ?

there was some reassortment(s) in the years before 1996 which reshuffled
the segments and formed the H5N1 from China.
We have no anchestor virus (we do have some H5N1 from America
and England <1996,BTW), but each single segment can be traced back.
I was talking about the 4th segment (HA of H5) above
and it seems to have a common origin with H2 in ~1750
and with H1 in ~1650 and with the H5 from 1959 in ~1955

 

[HenryN]

Re: since when is there influenza in humans ?

there was some reassortment(s) in the years before 1996 which reshuffled
the segments and formed the H5N1 from China.
We have no anchestor virus (we do have some H5N1 from America
and England <1996,BTW), but each single segment can be traced back.
I was talking about the 4th segment (HA of H5) above
and it seems to have a common origin with H2 in ~1750
and with H1 in ~1650 and with the H5 from 1959 in ~1955

Reassortment doesn't changes sequences (by DEFINITION), no matter how many times you post the same nonsense.

 

[gsgs]

Re: since when is there influenza in humans ?

it seems that today's influenza is not so old.
Two segments of the same type don't have a most recent common anchestor
of before 1800.
So, maybe there was one big bird-panzootic somewhere between
1750 and 1850 which wiped out almost all previous influenza
and which is the anchestor of all today's flu, avian human and swine.
Except for the different types of HAs and NAs and NSs, of course.
(usually 16 HAs and 9 NAs are distinguished, but there are really also
2 different NSs)
These are too different from each other as that they could have a MRCAD of >1800.

The similarity and relationship in the segments can best be seen
by comparing with 1918 panflu and with modern H1N1 :
All segments within the same type (1,1,1,16,1,9,1,2) are
either descendants of 1918 panflu ( ==> human or swine)
or are significantly closer to the 1918 virus than to the
modern H1N1, which evolved away from the 1800 consensus.

I didn't find a full bird-segment, which has more differences from 1918-H1N1
than 2007-(human)H1N1.
Except the Nanchang quail from 2000, which has clearly got it from a
mammal.

Now, what was before the panzootic big bang in ~1800 ?
Maybe entirely different types in the segments other than HA,NA,NS too ?

---------edit--------
there are some few equine viruses which seem to be older in segments 7,8
than other flu, with a MRCAD of maybe before 1800

------edit-------
I also checked some HA now. It can be clearly seen that H1 and H5 are drifting
away from each other, also H1 and H2, H1 and H5 in 278 out of 295 sequences,
which are closer to 1918 H1N1 than 2007 H1N1.
This suggests a common origin of those HAs. H5 is most similar to H2, H1 to H2,H5,H6.
That common origin however clearly predates 1800, at which time the inner
segments had their common anchestor.

-----edit----
a quick calculation gives about 1810,1780,1835,1830,1830,1830,1840,1840 for the common
origin in the segments 1,2,3,41,5,61,7,81 (+-20 years)
someone please check and confirm !


bad sequences:

1833,1947, 3648 2280 418 2280 444 A/equine/Prague/1/1956(H7N7)
1804,2001, 3137 2278 411 2278 456 A/chicken/Jilin/ho/2003(H5N1) nonfunct
1798,1979, 495 2263 407 2263 448 A/chicken/Chile/4957/02(H7N3)
1769,1941, 2931 2040 361 2040 396 A/swine/Henan/3/2004(H9N2)
1763,1953, 494 2263 399 2263 442 A/chicken/Chile/176822/02(H7N3)

1860,2005, 5251 2274 423 2274 456 A/TW/229/03(H3N2)
1811,1952, 4420 2274 412 2274 444 A/Canterbury/258/2005(H3N2)

1698,1947, 2944 2131 362 2131 415 A/chicken/Jilin/ho/2003(H5N1) nonfunctional
1580,1867, 2942 1917 303 1917 358 A/chicken/Jilin/hm/2003(H5N1) nonfunctional
1562,1766, 867 2151 336 2151 380 A/shorebird/DE/68/2004(H13N9)

2316,2573, 1871 1701 394 1741 448 A/swine/Haseluenne/IDT2617/03(H1N1)) hemagglutinin mRNA, complete cds.
2292,2636, 733 1701 390 1737 458 A/swine/Spain/51915/2003(H1N1)) segment 4, complete sequence
2275,2651, 734 1701 387 1735 460 A/swine/Spain/53207/2004(H1N1)) segment 4, complete sequence
2275,2561, 311 1701 387 1718 440 A/swine/Cotes d'Armor/1455/99(H1N1)) H1HA gene for haemagglutinin, genomic RNA
2263,2590, 668 1701 385 1737 450 A/Swine/Spain/50047/2003(H1N1)) segment 4, complete sequence
2233,2481, 2077 1701 380 1741 432 A/Swine//Germany/1993(H1N1)
2208,2452, 309 1671 369 1668 409 A/swine/Italy/1498-2/97(H1N1)) H1HA gene for haemagglutinin, genomic RNA

1666,1994, 1639 1494 249 1494 298 A/shorebird/DE/68/2004(H13N9)
1653,1880, 4386 1494 247 1494 281 A/red-necked stint/Australia/2/2004(H4N8)
1632,2079, 5226 1476 241 1476 307 A/quail/Shantou/243/2000(H9N2)

2272,2750, 1517 1276 290 1276 351 A/chicken/Hubei/wi/1997(H5N1) nonfunctional
2111,2492, 1545 1350 285 1360 339 A/chicken/Jilin/xw/2003(H5N1)
2034,2500, 2382 1332 271 1332 333 A/Thailand/NKNP/2005(H5N1)
2010,2415, 2681 1333 268 1333 322 A/Thailand/NKFE/2005(H5N1)

1559,1997, 5304 821 128 821 164 A/chicken/Hunan/fg/2004(H5N1)
1459,1521, 6051 973 142 973 148 A/equine/Praque/1/56(H7N7)
1449,1500, 6105 973 141 973 146 A/swine/England/191973/92(H1N7)
1181,1325, 4481 973 115 973 129 A/red-necked stint/Australia/2/2004(H4N8)

1710,2093, 5837 836 143 836 175 A/equine/Detroit/3/1964(H7N7)
1686,2093, 5813 836 141 836 175 A/equine/Prague/1/1956(H7N7)
1423,1913, 5495 836 119 836 160 A/shorebird/Delaware/168/06(H16N3)

 

[gsgs]

Re: since when is there influenza in humans ?

no 1800 panzootic big bang.
I miscalculated. Maybe I can post a more exact calculation later.

Most pairs of segments have a MRCA of 1880 or later,
but 1918 panflu and fowl plague H7N1 in Dobson 1927
nave a MRCA in ~1840.

But there are clearly bottlenecks in avian influenza evolution,
not only these pandemics in humans which wipe out previous strains.
But the 16 HAs and 9NAs and 2 NSs survive the bottlenecks,
so is there just one sort of inner segments combining with all the
HAs and NAs at those times ?

 

[gsgs]

Re: since when is there influenza in humans ?

something, which bothers me since some weeks :


Chen and Holmes in
http://mbe.oxfordjournals.org/cgi/content/full/23/12/2336
only examine diversity within a serotype, but since flu reassorts
frequently general diversity within segments is more useful.

This is at most 26% in H1, 24% in N1, about 20% in the PB2,PB1,NP,NS(a),
19% in PA, 16% in MP.

Almost all of these viruses in all segments are closer to 1918(H1N1)
than to 2007(H1N1) suggesting a common origin with 1918(H1N1)
within the last few centuries.
This difference and its distribution suggests earliest MRCAs
in 1820,1840,1860,1900,1900,1910,?,? in the segments.
Evolution in segments 7,8 is unclear :
e.g. 1918/H1N1 has only 5% difference to
A/northern shoveler/California/HKWF383/2007(H6N1)
but 8% to 2007(H1N1)

However, there are at least two viruses escaping this
common origin:

A/Equine/Prague/1/1956(H7N7) segments 1,4,6,7,8
A/Chicken/Chile/4957/2002(H7N3) segments 1,4
+other viruses from Chile,Bolivia

A/Equine-Canine/Florida(H3N8) segments 2,3


these are some of the few ancient relicts who survived
the last bottleneck in the 19th century.
The mass of viruses was/is similar to A/Brevig/1918

All the other (>50000) are from the common group


the equine Prague virus has a particularly high AT-score
(6082 in PB2),
so it presumably went to mammals long ago (before 1850) and stayed
there without going back to birds.

The new equine/canine H3N8 has AT-score as human H3N2 (5715 vs. 5734
in PB2), that would suggest a separate evolution outside of
birds since at least 1900.

So the only avian flu outside the normal lineage, which
necked the bottle in the 19th century, is the Chile-Bolivia/2002.


Besides segments 4,6,8 where we have 16,9,2 different lineage,
which reassort with the other (bottleneck-) segments
since many centuries.

I had expected a more continuous evolution without bottlenecks in birds
in all segments.

What does it tell us about past and future pandemics ?
Pandemics usually start when some avian segments (involving HA)
reassort with 0-7 human segments and infect and adapt to humans.

The more different the segments from circulating human segments,
the more potentially dramatical the event.

However for the evolution of the flu, these mammalean escapades
are not important, the virus didn't "learn","adapt"
how to do this - it happens accidentally.


The question is, what triggers these Avian bottlenecks ?
Is it a new emerging dominant strain which wipes out
previous strains ? (as observed in human flu)
We haven't seen such an event since 150 year, so maybe
panzootics are more rare than human pandemics. (why ?)
What is the "feature" of these panzootics ?
Are ~30% of the bird-population infected as in human
pandemics ? How do they dominate and kill previous
strains with so many bird-species evolving separately ?

I don't understand this competition between flu-strains
with yearly human-flu bottlenecks.
Usually diversity should increase yearly but we typically see
one dominating strain, so we have little diversity
in e.g. human H3N2.

If we find such a bottleneck and kill it, would flu die ?
There are only a few independent introductions into
a country each year, why don't we have zero introductions
occasionally ?

 

[gsgs]

Re: since when is there influenza in humans ?

A/equine/Prague/1956(H7N7) and descendants (no samples
since 1977, but Webster said it's still around in segments 4,6,7)
have particularly hight AT-score, even more than influenza-B.
This suggests that this virus had been in mammals since centuries.
And it's the only such example which we have.
There are no close bird-sequences, so the virus presumably didn't
go back (?) to birds.
Where did it evolve all the time ? No reports about outbreaks in horses
until 1956. There was a big equizootic in 1872 and we have reports
that humans and horses often had the flu simultaneously in the
19th century. Maybe this virus or reassortants of it infected
humans in the past and then died.




AT-scores of selected viruses
total and in the 8 segments

5614  5592,5760,5708,5778,5357,5716,5213,5453,  -  >A/Index/early human/~1935(H1N1)
5574  5561,5659,5620,5802,5310,5751,5152,5465,  -  >A/Brevig Mission/1/1918(H1N1)
5611  5592,5703,5685,5837,5317,5829,5152,5465,  -  >A/Index/early swine/~1935(H1N1)

5505  5531,5659,5674,----,5220,----,5150,----,  -  >A/duck/Memphis/546/1974(H11N9)
5720  ----,----,----,5767,----,5652,----,----,  -  >A/Anas crecca/Spain/1384/2007(H1N1)
5506  5472,5642,5723,----,5214,----,5170,5584,  -  >A/Index/7 birds similar to BM18/~1975
5556  5417,5756,5535,5830,5285,5770,5110,5543,  -  >A/pintail/Alaska/20/2005(H12N5)
5569  5574,5753,5620,5696,5258,5594,5121,5719,  -  >A/mallard/Interior Alaska/2/2007(H4N6)
5560  5510,5732,5655,5655,5234,5659,5183,5649,  -  >A/pintail/Alaska/279/2005(H3N8)
5570  5547,5742,5656,5649,5226,5665,5216,5649,  -  >A/mallard/Alaska/715/2005(H3N8)
5737  5729,5798,5797,5821,5519,5986,5309,5745,  -  >A/duck/LA/17G/1987(H3N8)
6087  6073,6167,6270,6199,5850,6176,5483,6187,  -  >A/equine/Lexington/1-1/1966(H7N7)
6016  ----,----,----,----,5814,6152,----,6150,  -  >A/equine/Prague/1-3/1956(H7N7)
5978  6091,5533,----,6216,5814,6713,5530,6191,  -  >A/equine/Prague/1-1/1956(H7N7)
5897  ----,----,----,----,5725,6142,5550,6191,  -  >A/equine/Prague/1-2/1956(H7N7)
5733  5594,5606,5735,6203,5267,6184,5570,5777,  -  >A/equine/Kentucky/1a/1975(H7N7)
5548  5526,5540,5652,5797,5272,5624,5131,5710,  -  >A/equine/Uruguay/1/1963(H3N8)
5733  5681,5728,5893,5959,5444,5890,5248,5849,  -  >A/swine/Chibi/01/2005/12/15(H3N8)

5621  5723,5743,5741,5543,5384,5687,5236,5627,  -  >1968//,182,CHN,A/Beijing/1/68
5615  5666,5751,5741,5584,5357,5673,5226,5675,  -  >1972//,1643,RUS,A/Udorn/307/72
5641  5710,5769,5788,5617,5357,5695,5241,5663,  -  >1979//,4199,THA,A/Bangkok/01/79
5643  5706,5756,5783,5673,5344,5702,5224,5675,  -  >1983//,5660,HKG,A/HK/14/83
5654  5701,5783,5783,5667,5384,5677,5259,5722,  -  >1989//,7852,CHN,A/Beijing/353/89
5665  5736,5773,5778,5720,5364,5702,5248,5746,  -  >1997/11/29,10924,USA,A/NY/503/97
5674  5728,5760,5736,5784,5437,5687,5243,5817,  -  >2007/02/06,14278,AUS,A/Brisbane/10/07

6087  6073,6167,6270,6199,5850,6176,5483,6187,  -  >A/equine/Lexington/1-1/1966(H7N7)
5990  6071,6179,6166,5774,5765,5746,6138,5964,  -  >B/Mississippi/UR06-0031/2007

5574  5561,5659,5620,5802,5310,5751,5152,5465,  -  >A/Brevig Mission/1/1918(H1N1)
5587  5578,5681,5639,5778,5310,5808,5142,5477,  -  >A/swine/Jamesburg/1942(H1N1)
5663  5684,5839,5741,5753,5370,5817,5158,5596,  -  >A/Denver/57(H1N1)
5691  5614,5848,5792,5978,5357,5851,5244,5489,  -  >A/New Jersey/1976(H1N1)
5669  5671,5826,5750,5843,5283,5810,5274,5584,  -  >A/Index/1977(H1N1)
5742  5820,5897,5834,5812,5384,5866,5366,5596,  -  >A/Kansas/UR06-0068/2007(H1N1)
5632  5526,5800,5578,5920,5377,5794,5285,5608,  -  >A/Mexflu/index/2009-02-01