H7N9 Discussion - from September 2014 on

JJackson · Sep 4, 2014

I have opened this new thread, and closed the old one, in anticipation of this year's H7N9 'season' in China - assuming it stays there.
The previous threads can be found here

H7N9 – Discussion, April 1, 2013 to June 3, 2013 (Closed)

&

H7N9 discussion thread: January 24, 2014 to Feb 5 2014 (closed)

This WHO graph show the weekly cases over the previous two periods and we are beginning to see the odd case already this season.

We are now in week 36 of 2014 and are likely to see a, hopefully, gradual increase in numbers over the next months.

Wet markets were blamed for much of the problem last year and the Chinese government was to implement a plan to phase them out and increase the slaughter house capacity. I have heard little about this during the 'off' season and hope it has not been neglected as it is no small project with such a large portion of the nations poultry traditionally sold in this way. If anyone has seen updates on this I would be grateful for any links.

With the potential for an Ebola Pandemic garnering so much attention it is important we do not take our eyes of this ball. Last year was the first full season - as the first human case did not occur until late in the previous N. Hemisphere season (week 8 of 2013).
The sporadic 'off season' cases indicate that this virus is still circulating in its natural host(s) and unless it is handled significantly more effectively this time there is little reason to expect anything but a similar distribution to last years graph.

The question becomes 'while the shape remains the same will the scale be similar?'. If we can not 'shrink' the number of human cases H7N9 will continue to adapt to its new host and we risk a new flu pandemic but this time, unlike H1N1(2009), it is unlikely to be relatively mild.

gsgs · Sep 5, 2014

Re: H7N9 Discussion - from September 2014 on

I thought the H7N9-season starts in Dec. and then speeds up
on Chinese New Year

have they figured out why the age and sex distribution
still S+E China ?

what if we add amino acids to the cleavage site

number of avian genomes uploaded to genbank per year in 2000,...,2014:
1,3,8,24,18,61,465,301,337,473,697,749,881,2099,1501(sofar)

# H5 cleavage site by length : 1108,11,49,1402,3388
# H7 cleavage site by length : 1651,1,60,26,85

JJackson · Sep 5, 2014

Re: H7N9 Discussion - from September 2014 on

gsgs said:
I thought the H7N9-season starts in Dec. and then speeds up
on Chinese New Year

have they figured out why the age and sex distribution
still S+E China ?

what if we add amino acids to the cleavage site

gs looking at last year, in the graph above, it seems to started in week 41 and run through to week 25 of the following year. As there had been a lull in the old thread and there are 2 new cases just confirmed this seemed like a reasonable time to start thinking about this season.

I did not know about the sex differential in the SE can you give a link?

as to the cleavage site are you talking about the addition of basic AAs causing an LP to HP change? I have not seen any data suggesting that was occurring although the emergence of an HPAI H5N6 is definitely concerning. On H5N6 have you looked at any sequences and has the H5 come from an H5N1 lineage?

gsgs · Sep 6, 2014

Re: H7N9 Discussion - from September 2014 on

I found one H5N6 genome at genbank:
>KJ754142,A/duck/Guangdong/GD01/2014,2014/03/,China,H5N6,Avian

it has 20,10,16,--,11,--,16,27 differences from the bird index.
Pretty much, it's probably a poultry virus in all 8 segments.
segments 1,2,3,4,5,7,8 from H5N1 in Vietnam and
segment 6 from H6N6 which is circulating in South China since years.
HA, segment 4 is maybe from yet another slightly different H5N1 strain
also going into H5N8
Compare with the ducks from Bangladesh and the recent H5N8
in the H5N1-thread, http://www.flutrackers.com/forum/showpost.php?p=545026
they are less poultry-like in segments 1,2,3,5,8

closest matches:

Code:

>KJ754142,A/duck/Guangdong/GD01/2014,2014/03/,China,H5N6,Avian
----------segment 1------------- 
 149   34 2280 6933 >CY146697,A/duck/Hunan/S4220/2011,2011/11/13,China,H5N1,Avian,1
 188   43 2280  424 >AB824276,A/duck/Quang Ninh/21/2013,2013/04/10,Viet Nam,H5N1,Avian,1
 192   44 2280  428 >AB828586,A/duck/Quang Ninh/53/2013,2013/05/09,Viet Nam,H5N1,Avian,1
 192   44 2280  429 >AB828690,A/muscovy duck/Quang Ninh/49/2013,2013/05/09,Viet Nam,H5N1,Avian,1
 210   48 2280  349 >AB741563,A/muscovy duck/Vietnam/LBM66/2011 ,2011/12/06,Viet Nam,H5N1,Avian,1
 210   48 2280 11786 >JX534594,A/wild duck/Fujian/2/2011,2011/03/11,China,H5N1,Avian,1
 210   48 2280 12600 >KF735641,A/barn swallow/Hong Kong/1161/2010,2010/03/29,Hong Kong,H5N1,Avian,1
 214   49 2280 11785 >JX534586,A/wild duck/Fujian/1/2011,2011/03/10,China,H5N1,Avian,1
 250   57 2280 11451 >JN646693,A/duck/Zhejiang/224/2011,2011/02/,China,H5N1,Avian,1
  328   75 2280 2352 >CY036242,A/grey heron/Hong Kong/1046/2008,2008//,Hong Kong,H5N1,Avian,1
----------segment 2------------- 
 171   39 2274 11384 >JN646700,A/duck/Zhejiang/224/2011,2011/02/,China,H5N1,Avian,2
 171   39 2274 11385 >JN646701,A/duck/Zhejiang/2242/2011,2011/02/,China,H5N1,Avian,2
 171   39 2274 11386 >JN646702,A/duck/Zhejiang/2243/2011,2011/02/,China,H5N1,Avian,2
 171   39 2274 11387 >JN646703,A/duck/Zhejiang/2244/2011,2011/02/,China,H5N1,Avian,2
 171   39 2274 11389 >JN646705,A/duck/Zhejiang/2248/2011,2011/02/,China,H5N1,Avian,2
 189   43 2274 12540 >KF735642,A/barn swallow/Hong Kong/1161/2010,2010/03/30,Hong Kong,H5N1,Avian,2
 197   45 2274 11383 >JN646699,A/duck/Zhejiang/213/2011,2011/02/,China,H5N1,Avian,2
 211   48 2274 11737 >JX534595,A/wild duck/Fujian/2/2011,2011/03/11,China,H5N1,Avian,2
 215   49 2274 11736 >JX534587,A/wild duck/Fujian/1/2011,2011/03/10,China,H5N1,Avian,2
 224   51 2274 12713 >KJ484617,A/duck/Hunan/749/2011,2011/12/28,China,mixed,Avian,2
 228   52 2274 12712 >KJ484607,A/duck/Hunan/747/2011,2011/12/28,China,mixed,Avian,2
----------segment 3------------- 
 120   26 2151 6880 >CY146699,A/duck/Hunan/S4220/2011,2011/11/13,China,H5N1,Avian,3
 148   32 2151 12505 >KF735643,A/barn swallow/Hong Kong/1161/2010,2010/03/31,Hong Kong,H5N1,Avian,3
 162   35 2151 11432 >JN646707,A/duck/Zhejiang/224/2011,2011/02/,China,H5N1,Avian,3
 162   35 2151 11433 >JN646708,A/duck/Zhejiang/2242/2011,2011/02/,China,H5N1,Avian,3
 162   35 2151 11434 >JN646709,A/duck/Zhejiang/2243/2011,2011/02/,China,H5N1,Avian,3
 162   35 2151 11435 >JN646710,A/duck/Zhejiang/2244/2011,2011/02/,China,H5N1,Avian,3
 162   35 2151 11437 >JN646712,A/duck/Zhejiang/2248/2011,2011/02/,China,H5N1,Avian,3
 176   38 2151 11431 >JN646706,A/duck/Zhejiang/213/2011,2011/02/,China,H5N1,Avian,3
 185   40 2151 2279 >CY036244,A/grey heron/Hong Kong/1046/2008,2008//,Hong Kong,H5N1,Avian,3
 190   41 2151 11760 >JX534588,A/wild duck/Fujian/1/2011,2011/03/10,China,H5N1,Avian,3
 195   42 2151 11761 >JX534596,A/wild duck/Fujian/2/2011,2011/03/11,China,H5N1,Avian,3
 204   44 2151 2275 >CY036212,A/grey heron/Hong Kong/3088/2007,2007//,Hong Kong,H5N1,Avian,3
 204   44 2151 2280 >CY036252,A/magpie robin/Hong Kong/1097/2008,2008//,Hong Kong,H5N1,Avian,3
 204   44 2151 2281 >CY036260,A/magpie robin/Hong Kong/1897/2008,2008//,Hong Kong,H5N1,Avian,3
 213   46 2151 2278 >CY036236,A/great egret/Hong Kong/807/2008,2008//,Hong Kong,H5N1,Avian,3
----------segment 4------------- 
 234   40 1704 4910 >JX534565,A/wild duck/Shandong/628/2011,2011/04/14,China,H5N1,Avian,4
 240   41 1704 4851 >JQ973694,A/duck/Jiangsu/k1203/2010,2010/12/05,China,H5N8,Avian,4
 264   45 1704 4756 >JQ041402,A/goose/Eastern China/1112/2011,2011/01/,China,H5N2,Avian,4
 275   47 1704 4904 >JX507355,A/duck/Jiangsu/m234/2012,2012/01/18,China,H5N2,Avian,4
 281   48 1704 4755 >JQ041401,A/duck/Eastern China/1111/2011,2011/01/,China,H5N2,Avian,4
 299   51 1704 5215 >KJ413834,A/breeder duck/Korea/Gochang1/2014,2014/01/16,South Korea,H5N8,Avian,4
 328   56 1704 1371 >CY091635,A/duck/Guangdong/wy19/2008,2008/06/06,China,H5N5,Avian,4
 328   56 1704 5221 >KJ476670,A/duck/Zhejiang/6D18/2013,2013/12/14,China,H5N8,Avian,4
 334   57 1704 5220 >KJ476669,A/duck/Zhejiang/W24/2013,2013/11/14,China,H5N8,Avian,4
 352   60 1704 1370 >CY091627,A/duck/Guangdong/wy11/2008,2008/06/06,China,H5N5,Avian,4
 357   61 1704 4989 >KC631941,A/chicken/China/AH/2012,2012/09/05,China,H5N1,Avian,4
 357   61 1704 5216 >KJ413842,A/broiler duck/Korea/Buan2/2014,2014/01/17,South Korea,H5N8,Avian,4
 357   61 1704 5217 >KJ413850,A/baikal teal/Korea/Donglim3/2014,2014/01/17,South Korea,H5N8,Avian,4
 363   62 1704  336 >AB932556,A/chicken/kumamoto/17/2014,2014/04/13,Japan,H5N8,Avian,4
 375   64 1704 4191 >GU727661,A/duck/Eastern China/031/2009,2009/01/15,China,H5N5,Avian,4
 410   70 1704 4190 >GU727653,A/duck/Eastern China/008/2008,2008/12/15,China,H5N5,Avian,4
 416   71 1704 4192 >GU727669,A/duck/Eastern China/108/2008,2008/12/15,China,H5N1,Avian,4
----------segment 5------------- 
 180    3  166 8251 >DQ493137,A/duck/Vietnam/S649/2005,2005//,Viet Nam,H5N1,Avian,5
 180   27 1497 6385 >CY146701,A/duck/Hunan/S4220/2011,2011/11/13,China,H5N1,Avian,5
 193   29 1497 11095 >JN646721,A/duck/Zhejiang/224/2011,2011/02/,China,H5N1,Avian,5
 193   29 1497 11097 >JN646723,A/duck/Zhejiang/2243/2011,2011/02/,China,H5N1,Avian,5
 193   29 1497 11098 >JN646724,A/duck/Zhejiang/2244/2011,2011/02/,China,H5N1,Avian,5
 193   29 1497 11100 >JN646726,A/duck/Zhejiang/2248/2011,2011/02/,China,H5N1,Avian,5
 200   30 1497 11094 >JN646720,A/duck/Zhejiang/213/2011,2011/02/,China,H5N1,Avian,5
 200   30 1497 11096 >JN646722,A/duck/Zhejiang/2242/2011,2011/02/,China,H5N1,Avian,5
 200   30 1497 12390 >KJ484611,A/duck/Hunan/747/2011,2011/12/28,China,mixed,Avian,5
 200   30 1497 12391 >KJ484621,A/duck/Hunan/749/2011,2011/12/28,China,mixed,Avian,5
 207   16  770  349 >AB780487,A/duck/Vietnam/OIE-2236/2012,2012/08/11,Viet Nam,H5N1,Avian,5
 207   31 1497 6386 >CY146709,A/duck/Hunan/S4234/2011,2011/11/13,China,H5N1,Avian,5
 213   32 1497  361 >AB786685,A/muscovy duck/Vietnam/LBM228/2012,2012//,Viet Nam,H5N1,Avian,5
----------segment 6------------- 
 340   47 1380  643 >CY109764,A/duck/Shantou/1984/2007,2007/08/,China,H6N6,Avian,6
 417   42 1005  681 >CY109994,A/duck/Shantou/13629/2006,2006/07/,China,H6N6,Avian,6
 431   52 1206  680 >CY109992,A/duck/Shantou/13252/2006,2006/07/,China,H6N6,Avian,6
 466   47 1007  673 >CY109970,A/duck/Shantou/7412/2006,2006/04/,China,H6N6,Avian,6
 466   49 1050  671 >CY109966,A/duck/Shantou/6212/2006,2006/03/,China,H6N6,Avian,6
 470   48 1020  666 >CY109950,A/duck/Shantou/4052/2006,2006/02/,China,H6N6,Avian,6
 482   50 1037  672 >CY109968,A/duck/Shantou/6270/2006,2006/03/,China,H6N6,Avian,6
 528   73 1380  628 >CY109492,A/duck/Fujian/958/2006,2006/01/,China,H6N6,Avian,6
 650   69 1061  774 >CY110520,A/duck/Fujian/5614/2007,2007/10/,China,H6N6,Avian,6
1257  148 1177  422 >CY077435,A/duck/Victoria/2001,2001//,Australia,H4N6,Avian,6
----------segment 7------------- 
 101   10  982 6901 >CY146703,A/duck/Hunan/S4220/2011,2011/11/13,China,H5N1,Avian,7
 112   11  982 11963 >JN646735,A/duck/Zhejiang/224/2011,2011/02/,China,H5N1,Avian,7
 112   11  982 11964 >JN646736,A/duck/Zhejiang/2242/2011,2011/02/,China,H5N1,Avian,7
 112   11  982 11965 >JN646737,A/duck/Zhejiang/2243/2011,2011/02/,China,H5N1,Avian,7
 112   11  982 11966 >JN646738,A/duck/Zhejiang/2244/2011,2011/02/,China,H5N1,Avian,7
 112   11  982 11968 >JN646740,A/duck/Zhejiang/2248/2011,2011/02/,China,H5N1,Avian,7
 112   11  982 12480 >KC436114,A/oriental magpie robin/Hong Kong/470.1/2011,2011//,Hong Kong,H5N1,Avian,7
 115   10  866  418 >AB780497,A/duck/Vietnam/OIE-2212/2012,2012/08/11,Viet Nam,H5N1,Avian,7
 122   12  982 11962 >JN646734,A/duck/Zhejiang/213/2011,2011/02/,China,H5N1,Avian,7
 122   12  982 12482 >KC436117,A/brown-headed gull/Hong Kong/709/2011,2011//,Hong Kong,H5N1,Avian,7
 122   12  982 12483 >KC436118,A/large billed crow/Hong Kong/497/2011,2011//,Hong Kong,H5N1,Avian,7
 132   13  982  366 >AB741569,A/muscovy duck/Vietnam/LBM66/2011 ,2011/12/06,Viet Nam,H5N1,Avian,7
----------segment 8------------- 
 133   11  821 8887 >CY146704,A/duck/Hunan/S4220/2011,2011/11/13,China,H5N1,Avian,8
 182   15  821 10115 >KF735646,A/barn swallow/Hong Kong/1161/2010,2010/04/03,Hong Kong,H5N1,Avian,8
 207   17  821 10053 >JX534593,A/wild duck/Fujian/1/2011,2011/03/10,China,H5N1,Avian,8
 207   17  821 10054 >JX534601,A/wild duck/Fujian/2/2011,2011/03/11,China,H5N1,Avian,8
 219   18  821 10108 >KF182745,A/duck/Vietnam/QB1207/2012,2012/07/28,Viet Nam,H5N1,Avian,8
 219   18  821 10170 >KJ484615,A/duck/Hunan/747/2011,2011/12/28,China,mixed,Avian,8
 219   18  821 10171 >KJ484625,A/duck/Hunan/749/2011,2011/12/28,China,mixed,Avian,8
 219   18  821 8211 >AB786680,A/muscovy duck/Vietnam/LBM227/2012,2012//,Viet Nam,H5N1,Avian,8
 219   18  821 8212 >AB786688,A/muscovy duck/Vietnam/LBM228/2012,2012//,Viet Nam,H5N1,Avian,8

JJackson · Sep 6, 2014

Re: H7N9 Discussion - from September 2014 on

Thanks for checking that out gs. And apologies to all for the large graph which caused some users to get a side-scroll. I have reduced it to a more sensible size.

gsgs · Sep 8, 2014

Re: H7N9 Discussion - from September 2014 on

> as to the cleavage site are you talking about the addition of basic
> AAs causing an LP to HP change? I have not seen any data
> suggesting that was occurring

I mean, they should test it in the lab. In chickens,ducks,ferrets or mice.
In many (most ?) H5 or H7 outbreaks in chickens in the past we did see
the HP change after some months or years.
So we should prepare for this. Would it be even more virulent in humans ?
Does it transmit in chickens ?
Is it even desirable since that makes it easier to detect H7N9 ?
We could do it in the lab and spread the new HP H7N9 in poultry markets
so to replace the LP variant by immunity competition

-------------------------------------------------------------
http://www.pubfacts.com/author/Jessica+Bogs
http://www.pubfacts.com/detail/2489...rulence-Study-in-Chickens-Pigeons-and-Ferrets.
novel H7N9 and recent European H7N7 induced no signs of disease despite substantial replication
in inoculated chickens and rapid transmission to contact chickens.
Evidence of the replication of both viruses in pigeons, albeit at lower levels of RNA excretion
In ferrets greater replication of H7N9 than of H7N7 with significant differences in viral presence
e.g. in nasal wash, lung, and cerebellum samples. Both could potentially spread to the brain.

H9 avian influenza reassortant with engineered polybasic cleavage site displays a highly pathogenic phenotype in chicken.
Acquisition of a polybasic hemagglutinin cleavage site by a low-pathogenic avian influenza virus is not sufficient for immediate transformation into a highly pathogenic strain.
-----------------------------------------------------------------

JJackson · Sep 8, 2014

Re: H7N9 Discussion - from September 2014 on

gs I am shocked. I would never have expected to see you advocating a 'gain of function' experiment.

I would be very much against introducing an kind of experimental virus into the gene pool on the grounds we just don't know enough to be sure nature would not find a way of using the new sequences to create an even big problem. Added to which it could have disastrous consequences for the food supply if the HP variant supplanted the LP strain as the wild type in the non poultry host(s).

In humans the HP change would increase tissue tropism - assuming no other effects - which can not be a good thing.

gsgs · Sep 8, 2014

Re: H7N9 Discussion - from September 2014 on

why should gof be bad ? We'd like to know. But we shouldn't publish critical results.
If that gof is bad for chickens but good for humans then we should consider it.
As we should consider making circulating flu-strains less virulent.
Suppose we figure out how to make a strain less virulent, is it ethical to _not_ do it ?
Yes, there is some risk, but the risk from doing nothing would be reasonably considered bigger.
In our legal system doing risk is punished, but reducing risk by the same amount
isn't rewarded by the same amount. So people/companies are reluctant to do it.

Also, this "gof" is one, that may well occur in nature, in chickens.
We have lots of examples for that.

Laidback Al · Sep 8, 2014

Re: H7N9 Discussion - from September 2014 on

Given the recent biolab breaches, I think we should be skeptical of scientists being able to undertake gain of function (GOF) research without mistakes or escapes. Even if successful, the interplay of human intervention and natural selection could have unintended consequences. Humans have been trying to control the natural environment for a long time and look how well that has worked out.

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sharon sanders · Sep 8, 2014

Re: H7N9 Discussion - from September 2014 on

It has gone about as well as all the groups who claim their computer program can predict disease outbreaks. Not one novel disease outbreak has been predicted by any human or computer - ever.

gsgs · Sep 8, 2014

Re: H7N9 Discussion - from September 2014 on

the question is not whether we should do gof-research but rather how much
and how much safety we should require.
And what of it we should publish

H7N9 Discussion - from September 2014 on

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