Re: Where H1N1 began La Gloria considered Town Zero in outbreak of H1N1 strain
well, it still reassorts .... especially in swine
But generally, the longer one strain envolves in mammals or poultry, the more it drifts away from the
avian consensus and the more different two viruses are, the less likely they reassort.
(in general,imo)
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Re: Where H1N1 began La Gloria considered Town Zero in outbreak of H1N1 strain
Sorry I missed your response, gsgs. That could certainly be the answer. I see the authors of that paper suggested looking at other strains:
There's a paper citing that one now and it gives me the impression that a shift in human flu viruses took place after the 90's that made them less likely to reassort, at least in vaccine manufacturing conditions:No reassortant containing a gene constellation similar to that of pH1N1 virus was found in either coinfected cells or pigs, indicating that the reassortment event that resulted in the generation of this virus is a rare event that likely involved specific viral strains and/or a favorable, not-yet-understood environment.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133923/
So it makes me wonder if both swine and human viruses were generally resistant to reassortment in 2009?Contribution of Neuraminidase of Influenza Viruses to the Sensitivity to Sera Inhibitors and Reassortment Efficiency
Irina Kiseleva, Natalie Larionova, Ekaterina Fedorova, Ekaterina Bazhenova, Irina Dubrovina, Irina Isakova-Sivak, Larisa Rudenko
Open Microbiol J. 2014; 8: 59?70. Published online 2014 July 11. doi: 10.2174/1874285801408010059
...
LAIV strain development and characterization takes at least 2.5-3 months, and is a reasonably complicated and difficult process. Successful and fast generation and characterization of vaccine reassortants depends on numerous factors. In this study we show that most influenza A and B viruses that circulated in the 1990s readily reassorted with MDVs, and reassortants with the desired vaccine genotype were easy to generate. The majority of the resulting reassortants inherited all internal genes from MDVs and HA and NA from WT parental viruses. In contrast, vaccine strains based on most recently circulating viruses were much more difficult to develop. Only 11-14% of reassortants possessed NA from the WT parental virus, and the percentage of internal genes derived from MDVs was relatively low.
...
A little is known about an efficacy of reassortment in vitro or in vivo. Some pairs of viruses are difficult to reassort, as seen in attempts to generate avian-human reassortant viruses with the desired genomic composition. Subarrao et al. [22] obtained 6:2 reassortants of H3N2 human virus with gull influenza A virus, but the attempt to generate 6:2 reassortants of H1N1 human viruses with the same gull influenza A virus was not successful. The authors suggested that some influenza virus gene segments appear to be incompatible for generation of reassortants.
Indeed, reassortment, especially obtaining reassortants with desired gene combinations (6:2, for instance) is really rare event. In recent publication [23] interesting observation was made that pandemic ?H1N1 virus could not be reproduced either in cell cultures or in pigs coinfected with North American triple reassortant H1N1 and Eurasian H1N1 swine influenza viruses.?
Molecular basis of such restriction is still unknown. We can only speculate that the nature of this process depends on combination of as yet unknown factors...Leave a comment:
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Re: Where H1N1 began La Gloria considered Town Zero in outbreak of H1N1 strain
they just tested 2 strains:
A/Swine/Spain/53207/2004(SP04),
A/Swine/Kansas/77778/2007(KS07)
I'd try Tx/4199-2 and England/1993,
you's need another reassortment then to pick H1-HA
or start from the Wisconsin man, WI/10/1998
--------------------------------------------
Code:>A/******/index/2009/02/01 ------------segment 1------------------------ 293 67 2279 775 >CY095672,A/swine/Texas/4199-2/1998,1998//,USA,H3N2,Swine,1 -------------segment 2----------------------------- 338 77 2274 803 >CY095673,A/swine/Texas/4199-2/1998,1998//,USA,H3N2,Swine,2 -------------segment 3---------------------------- 344 74 2151 782 >CY095674,A/swine/Texas/4199-2/1998,1998//,USA,H3N2,Swine,3 ------------segment 4--------------------- 447 76 1700 76 >AF455680,A/Swine/Indiana/P12439/00 ,2000//,USA,H1N2,Swine,4 452 77 1700 519 >GQ229365,A/swine/Hong Kong/NS623/2002,2002/07/09,Hong Kong,H1N2,Swine,4 458 78 1700 47 >AF250124,A/Swine/Indiana/9K035/99 ,1999//,USA,H1N2,Swine,4 464 79 1700 799 >CY085622,A/swine/Hong Kong/NS30/2004,2004/01/06,Hong Kong,H1N2,Swine,4 --------------segment 5-------------------------- 293 44 1497 850 >CY095676,A/swine/Texas/4199-2/1998,1998//,USA,H3N2,Swine,5 -------------segment 6------------------- 588 83 1410 969 >CY116038,A/swine/England/195852/1992,1992/01/07,United Kingdom,H1N1,Swine,6 --------------segment 7--------------------------- 163 4 245 552 >FJ975097,A/swine/Italy/306907/2003,2003/12/,Italy,H1N1,Swine,7 228 22 964 127 >AY363573,A/swine/Hong Kong/5190/99,1999//,Hong Kong,H3N2,Swine,7 336 33 982 1092 >CY116138,A/swine/England/375017/1993,1993/10/24,United Kingdom,H3N2,Swine,7 -------------segment 8----------------------------- 346 29 838 864 >CY095679,A/swine/Texas/4199-2/1998,1998//,USA,H3N2,Swine,8 1 >A/******/index/2009/02/01 5: 28, 31, 33,---, 29,---,115, 34 A/Sw/Index/triple-reassortant/1998(H3N2) 4: 33, 30, 43, 52, 36,201,119, 45 A/Wisconsin/10/98,1998//,H1N1 6: 29, 33, 34,---, 29,---,119, 34 A/swine/Texas/4199-2/1998,1998//,USA,H3N2,Swine 2: 36, 39, 43, 91, 34,200,125, 46 A/swine/North Carolina/47834/2000,2000//,USA,H1N1,Swine 3: 45, 47, 45, 91, 44,200,124, 51 A/Iowa/CEID23/2005,2005//,H1N1 7: 43, 48, 52,---, 44,---,120, 44 A/swine/Ontario/33853/2005(H3N2) 523 54 1032 287 >AF342821,A/Wisconsin/10/1998,1998//,USA,H1N1,Human,4 611 104 1701 2949 >FJ986620,A/Ohio/01/2007,2007/08/17,USA,H1N1,Human,4 611 104 1701 2950 >FJ986621,A/Ohio/02/2007,2007/08/17,USA,H1N1,Human,4 613 103 1679 2948 >FJ986619,A/Wisconsin/87/2005,2005/12/08,USA,H1N1,Human,4 793 135 1701 28 >L24362,A/Maryland/12/1991,1991//,USA,H1N1,Human,4 793 135 1701 81 >U53162,A/Wisconsin/4754/1994,1994//,USA,H1N1,Human,4 793 135 1701 82 >U53163,A/Wisconsin/4755/1994,1994//,USA,H1N1,Human,4 793 135 1701 3066 >CY039909,A/Maryland/12/1991,1991//,USA,H1N1,Human,4 799 136 1701 1229 >CY024925,A/Ohio/3559/1988,1988//,USA,H1N1,Human,4 898 152 1692 2947 >FJ986618,A/Iowa/01/2006,2006/11/08,USA,H1N1,Human,4 911 155 1701 747 >DQ889689,A/Iowa/CEID23/2005,2005//,USA,H1N1,Human,4 934 159 1701 3616 >JF758482,A/South Dakota/03/2008,2008/12/04,USA,H1N1,Human,4 file mx.n5
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Re: Where H1N1 began La Gloria considered Town Zero in outbreak of H1N1 strain
North American Triple Reassortant and Eurasian H1N1 Swine Influenza Viruses Do Not Readily Reassort to Generate a 2009 Pandemic H1N1-Like Virus
So how did it happen?
Leave a comment:
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Re: Where H1N1 began La Gloria considered Town Zero in outbreak of H1N1 strain
GCM settles in the valleys of Perote and Guadalupe Victoria. It has 16 farms in the border
states of Veracruz and Puebla
leading pork producer in Mexico, participating annually with 13% of national production,
equivalent to more than one million 200 thousand heads.
Welcome. Farms Carroll de Mexico (GCM) is a Mexican company
incorporated in 1993 with the aim of raising, marketing and processing cattle
pig...
in the late 1990s, after the North American Free Trade Agreement (NAFTA) opened up
Mexican markets to massive pork imports from US companies like Smithfield Foods,
Ortega and other small-scale butchers in Mexico were devastated by the drop in prices.
In 1993 Carroll Foods, a giant hog-raising corporation, partnered with a Mexican agribusiness
enterprise to set up a huge pig farm known as Granjas Carroll de Mexico (GCM) in Veracruz's
Perote Valley. Smithfield, which had a longtime partnership with Carroll Foods, bought the
company out in 1999.
--------------------------------------------------
best match of ****** in segment 6 is in English swine from 1992
so I seculate Granjas Carroll started with European swine (Spain ?)
in 1993. They were quite isolated, didn't mix with other swine.
The European virus kept infecting their pigs.
Then in 1999 they were bought by Smithfield, NAFTA was
implemented and they imprted US-swine which just had the
new triple-reassortant swine pandemic.
This 1998 virus is the best match of ****** in segments 1,2,3,4,5,8
Then at some time between 1999 and 2008 the strains reassorted
and ****** was created in swine at GCM.
It still didn't spread to other countries, there was not much
exchange of breeding pigs, they raised their own pigs.
Then in early 2009 some swine-worker was infected
and spread it to contacts and the pandemic started
(my speculation)
-------------------------------------------------------------------
2010 Mexican swine sequences in this thread:
-------------------------------------------------------------------Leave a comment:
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Re: Where H1N1 began La Gloria considered Town Zero in outbreak of H1N1 strain
the positions which you listed in post #10.
There my ******-index and my "******"-match index should coincide.
(I should have called it ******-ancestor)
Also Wisconsin/10, where available, or Sw/Nebraska/1998 in
segments 1,2,3,5,8
Sw/Germany/1981 or such in segments 6,7
There is one exception : 492A(7) . I think this is a coincidence.
****** mutated to G before 2009 and mutated back to A in April 2009Leave a comment:
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Re: Where H1N1 began La Gloria considered Town Zero in outbreak of H1N1 strain
Thanks for taking the time to look this over.Originally posted by gsgs View Post
Wisconsin/10/1998 is a bit problematic for me since it is only a partial genome. Not sure what you mean exactly by "critical positions" and how that relates to the ancients, but most of the Swine Flu mutations of interest have a history in H9N2 and H5N1 infected birds and humans in the Far East. It seems to me Swine Flu would be mutating away from the wild type characteristics that may have found their way into the swine population and moved toward an adaption to its new human host.
Let's keep working on the investigation, and keep an eye out for better information from some earlier infections in Mexico.Leave a comment:
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Re: Where H1N1 began La Gloria considered Town Zero in outbreak of H1N1 strain
sorry, mamabird, I had missed your earlier posts - too many threads here.
I suscribed now to this thread.
wrt. the original strain - you should consider what the ancestors had.
(e.g. Wisconsin/10 in segments 1,2,3,4,5,8)
---- or see my triple-reassortant-index which is also here:
http://www.h5n1experts.org/forum/showpost.php?p=1099 ---------
there had been a few hundred mutations since then (out of ~5000 relevant positions),
it would be very unlikely if just those mutations had been undone in the early
evolution of ******.
In almost all of the critical positions these ancestors coincide with my index-strain.
And my index-strain is the average of ~10 early strains.
Two independent, very strong arguments, IMO.Leave a comment:
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Re: Where H1N1 began La Gloria considered Town Zero in outbreak of H1N1 strain
GS: With regard to the evolution of H1N1 Swine Flu, I offer the following for your consideration of possible mutational events over a month?s time that might have led to the Cancun strain that seems to currently predominate. This reflects a logical progression of change from earliest available isolates to later sequences.Originally posted by Mamabird View Post
First assume that a very early Mexican virus is the possible starting point (Northern ? CDC variant ii). It is represented by CA/05 (3-30-09) and has the following genetic characteristics:
NS1: V123I (G0367A)
MP: Silent (A0492G and A0600G)
PB2: Silent (A2163G)
HA: T206S (A0658T)
HA: Silent (T1408C)
HA: Silent (C0022A)
NA: I106V and D247N (A0316G and G0742A)
NP: Silent (A1248G and A1143G)
NP: I100V and T373I (A0298G and T1118C)
PA: M582L (C1741A)
The first mutation is silent and represented by Mexico/4108 (4-03-09):
HA: A0022C
The second series of mutations (2) leading to Early Mex (CDC variant i) can be represented by Mexico/InDRE4487 (4-14-09):
NP: I373T (C1118T)
PA: L582M (A1741C)
The third series of mutations (5) leading to Pre-Cancun (CDC variant iii) can be represented by Mexico/4604 (4-19-09):
NA: V106I and N247D (G0316A and A0742G)
NP: V100I (G0298A)
NP: Silent (G1143A)
HA: Silent (C1408T)
The fourth series of mutations (6) leading to Cancun (CDC variant iv) can be represented by New York/06 (4-25-09):
NS1: I123V (A0367G)
HA: S206T (T0658A)
NP: Silent (G1248A)
MP: Silent (G0492A and G0600A)
PB2: Silent (G2163A)
This gives us 14 mutations in a very short period of time as the Swine Flu virus adapted to its new host. Since the end of April it seems to have been fairly stable. All of the other variations to date (Hamburg, Texas, Japan, Jersey for example) appear to have been self-limiting off-shoots from the strains above.
What do you think? Plausible?Leave a comment:
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Re: Where H1N1 began La Gloria considered Town Zero in outbreak of H1N1 strain
Helen Barnswell needs to ask the CDC at the weekly media briefing if their seroprevalence studies are available for public review. I would suspect that there is quite a bit of additional information of interest that is not yet in the public domain that could shed additional light on this historical discussion.Originally posted by gsgs View PostLeave a comment:
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Re: Where H1N1 began La Gloria considered Town Zero in outbreak of H1N1 strain
I think that we need to keep an open mind about this.Originally posted by gsgs View Post
Northern (CDC variant ii) might actually be the earliest viruses, and the markers that are lacking could be early mutations that became stable in the Swine Flu. I would suggest that these changes in the PA and NP segments went from wild type in the Northern viruses to human adapted form. We have to ask ourselves if Northern was not first, why the virus would mutate to the wild form. In addition, there is at least one HA silent marker in all viruses except Northern, once again supporting the theory that this was the first.
Let's talk further about this when time permits.Leave a comment:
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Re: Where H1N1 began La Gloria considered Town Zero in outbreak of H1N1 strain
why can't CDC and INDRE cooperate and examine this LaGloria etc.
as if it had happened on US-territory ?
We don't need borders, when the world-health is at stake.
The first case is the baby from St.Luis Potosi from
Feb.24 but we have no sequences. We have no serology from
LaGloria, whether that outbreak in Feb. was ******
We don't know who/where 4115 and 4487 are from.
And most important: we have no pig sequences. What strains
had been circulating in Mexican pigs in the last 10 years ?
What vaxes did they get ?
Is anything going to change wrt. pigflu surveillance ?Leave a comment:
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Re: Where H1N1 began La Gloria considered Town Zero in outbreak of H1N1 strain
Timelines can only be understood retrospectively. That is a fancy way of saying that we can only organized the sequence of events after the fact.I had assumed the first time I read it that they were talking about the US because we know the first cases were found in Mexico (don't we?).
The earliest known cases from March and possibly earlier did occur in Mexico. But at the time in late April when the official report in MMWR was published the authors believe they had a unique strain that had not been previously recognized. They were unaware that this novel strain was raging in Mexico. It was only later, after Mexican samples were sequenced in Canada, that it became clear that the two individuals reported in the MMWR article were infected with novel H1N1. There may have been other earlier infections in the United States, but these two will be recorded as the first two confirmed cases in the United States at the time of the report. I believe that are other individuals in the US who were infected with H1N1 earlier but only retrospectively confirmed later.Leave a comment:
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Re: Where H1N1 began La Gloria considered Town Zero in outbreak of H1N1 strain
Thanks Laidback Al for clearing that up.
Here is the first part of that section:So in the other paragraph I quoted, it again referred to:NHRC has identified 1939 cases of influenza A/H1N1v virus among active-duty (1270), DoD dependent (390) and US-Mexico border civilian (275) populations.I had assumed the first time I read it that they were talking about the US because we know the first cases were found in Mexico (don't we?). But each time I've read it, I just keep thinking it was strange they didn't specifically say: "US population" if that's what they meant.5 US-Mexico border clinics in San Ysidro, Calexico, Brawley, Tijuana, and Mexicali. The first identified case of influenza A/H1N1v in humans was identified in this population.
In the DOD reports, our military operations overseas are included in stats; so I didn't automatically assume the Navy report was only talking about the US when it said US/Mexico border civilian populations.
Admittedly, I've gone through several rolls of tinfoil with this pandemic. I probably used a 1/4 of a roll when I saw the Walter Reed Institute of Research had some sort of a submission connection to Mexico/47N.Leave a comment:
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Re: Where H1N1 began La Gloria considered Town Zero in outbreak of H1N1 strain
Originally posted by mixin View Post
That comment and the link refer to the first H1N1 officially recognized cases in the United States.Leave a comment:
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