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Where H1N1 began La Gloria considered Town Zero in outbreak of H1N1 strain

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  • gsgs
    replied
    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)

    Leave a comment:


  • Emily
    replied
    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:

    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.
    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:

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133923/
    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...
    So it makes me wonder if both swine and human viruses were generally resistant to reassortment in 2009?

    Leave a comment:


  • gsgs
    replied
    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

    Leave a comment:


  • Emily
    replied
    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:


  • gsgs
    replied
    Re: Where H1N1 began La Gloria considered Town Zero in outbreak of H1N1 strain

    http://www.granjascarroll.mx/
    http://www.granjascarroll.mx/en/1083-2/

    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...

    http://www.theinvestigativefund.org/...ed?page=entire
    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:
    http://www.flutrackers.com/forum/sho...d.php?t=191727

    -------------------------------------------------------------------

    Leave a comment:


  • gsgs
    replied
    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.
    http://www.h5n1experts.org/forum/showpost.php?p=1099
    (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 2009

    Leave a comment:


  • Mamabird
    replied
    Re: Where H1N1 began La Gloria considered Town Zero in outbreak of H1N1 strain

    Originally posted by gsgs View Post
    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.
    Thanks for taking the time to look this over.

    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:


  • gsgs
    replied
    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:


  • Mamabird
    replied
    Re: Where H1N1 began La Gloria considered Town Zero in outbreak of H1N1 strain

    Originally posted by Mamabird View Post
    I think that we need to keep an open mind about this.

    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.
    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.

    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:


  • Mamabird
    replied
    Re: Where H1N1 began La Gloria considered Town Zero in outbreak of H1N1 strain

    Originally posted by gsgs View Post
    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 ?
    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.

    Leave a comment:


  • Mamabird
    replied
    Re: Where H1N1 began La Gloria considered Town Zero in outbreak of H1N1 strain

    Originally posted by gsgs View Post
    > It’s here in La Gloria, three hours outside Mexico City, where it’s believed H1N1 made the
    > antigenic shift into humans.

    no. We have one early case from Feb.24 from Potosi.
    The La Gloria sequences already have the 2 Northern markers which
    other sequences are lacking (--> more original).
    .
    I think that we need to keep an open mind about this.

    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:


  • gsgs
    replied
    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:


  • Laidback Al
    replied
    Re: Where H1N1 began La Gloria considered Town Zero in outbreak of H1N1 strain

    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?).
    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.

    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:


  • mixin
    replied
    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:
    NHRC has identified 1939 cases of influenza A/H1N1v virus among active-duty (1270), DoD dependent (390) and US-Mexico border civilian (275) populations.
    So in the other paragraph I quoted, it again referred to:
    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.
    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.

    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:


  • Laidback Al
    replied
    Re: Where H1N1 began La Gloria considered Town Zero in outbreak of H1N1 strain

    Originally posted by mixin View Post
    I keep thinking about this comment from the US Navy site.

    Quote:
    Our CDC-BIDS collaborative border FRI surveillance program has resumed at 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.

    http://www.med.navy.mil/sites/nhrc/g.../FRIUpdate.pdf

    That comment and the link refer to the first H1N1 officially recognized cases in the United States.

    Leave a comment:

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