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Swine H9N2 - pandemic potential?

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  • #1

    Swine H9N2 - pandemic potential?

    Since surveillance for swine influenza with human potential is under discussion, I went looking for H9N2 pandemic potential in both avian and swine. A search of the NCBI database for H9N2/HA/swine returns 31 sequences (all in Asia) starting in 1998.

    Below are relevant articles:

    1: Vet Microbiol. 2008 Sep 18;131(1-2):82-92. Epub 2008 Mar 6.

    Isolation and genetic characterization of avian origin H9N2 influenza viruses from pigs in China.

    Yu H, Hua RH, Wei TC, Zhou YJ, Tian ZJ, Li GX, Liu TQ, Tong GZ.
    National Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, China.

    As pigs are susceptible to infection with both avian and human influenza A viruses, they have been proposed to be an intermediate host for the adaptation of avian influenza viruses to humans. In April 2006, a disease caused by highly pathogenic porcine reproductive and respiratory syndrome virus (PRRSV) occurred in several pig farms and subsequently overwhelmed almost half of China with more than 2,000,000 cases of pig infection. Here we report a case in which four swine H9N2 influenza viruses were isolated from pigs infected by highly pathogenic PRRSVs in Guangxi province in China.

    All the eight gene segments of the four swine H9N2 viruses are highly homologous to A/Pigeon/Nanchang/2-0461/00 (H9N2) or A/Wild Duck/Nanchang/2-0480/00 (H9N2). Phylogenetic analyses of eight genes show that the swine H9N2 influenza viruses are of avian origin and may be the descendants of A/Duck/Hong Kong/Y280/97-like viruses. Molecular analysis of the HA gene indicates that our H9N2 isolates might have high-affinity binding to the alpha2,6-NeuAcGal receptor found in human cells.

    In conclusion, our finding provides further evidence about the interspecies transmission of avian influenza viruses to pigs and emphasizes the importance of reinforcing swine influenza virus (SIV) surveillance, especially after the emergence of highly pathogenic PRRSVs in pigs in China.

    PMID: 18403137

    Here is a very good 23 page powerpoint presentation on the potential of H9N2 as regards birds. Couple that information with the above PubMed article on swine H9N2, and it's easy to see why Mamabird and others are reminding us that H9N2 bears close scrutiny.

    .
    "The next major advancement in the health of American people will be determined by what the individual is willing to do for himself"-- John Knowles, Former President of the Rockefeller Foundation
    Tags: h9n2, swine
  • #2
    Re: Swine H9N2 - pandemic potential?

    Researchers probe pandemic potential of H9N2 virus

    Lisa Schnirring Staff Writer

    Aug 14, 2008 (CIDRAP News) – Scientists have warned it's impossible to predict which avian influenza virus will spark the next pandemic, and while most of the attention has been on highly pathogenic H5N1, one research group is reporting new findings that raise concerns about the threat from the low-pathogenic H9N2 virus.

    The international group of researchers, mainly from the University of Maryland, published their findings in the August issue of PLoS One (Public Library of Science One). They used ferrets, which have sialic acid receptors in their respiratory tracts resembling those in humans, to explore how H9N2 viruses replicate and transmit.

    The H9N2 subtype has been found in many avian species in Asia, the Middle East, Europe, and Africa over the past decade, the authors write. The virus can cause mild-to-moderate disease in humans. In March 2007, Hong Kong officials reported that a 9-month-old girl was infected with the strain, the fourth time since 1999 that the virus was found in a child from that city.

    US officials have worried that H9N2 could evolve into a pandemic strain. In 2004, the National Institute of Allergy and Infectious Diseases (NIAID) contracted with Chiron Corp. (now part of Novartis) to produce a vaccine against the virus. In Sept 2006 researchers reported that the experimental vaccine generated a good immune response in a phase 1 clinical trial. The contract tapped Chiron to produce 40,000 doses of a vaccine containing an inactivated strain of H9N2 developed by the Centers for Disease Control and Prevention.

    The PLoS One report says that many H9N2 isolates have acquired human virus–like receptor specificity, preferentially binding alpha 2-6 sialic acid receptors.

    The authors write that three other factors also fuel concerns about the potential of H9N2 to evolve into a pandemic strain. Some studies have shown that H9N2 viruses extensively evolve and reassort, while others have shown that the viruses have spread to pigs, which could provide a "mixing vessel" with influenza viruses that are more likely to infect humans. Also, serologic studies have suggested that there may be more human cases of H9N2 than have been detected and reported so far.

    "Therefore, avian H9N2 viruses are in an ideal position to undergo further adaptation for more efficient transmission among mammals and humans," they write.

    In their study, the searchers first evaluated whether five wild-type H9N2 viruses could infect ferrets and whether infected animals could spread the disease to other ferrets through direct contact and through the air. Lethargy, anorexia, and temperature elevations were noted in some of the ferrets that were inoculated with the virus, and the virus was found in nasal washes from all the inoculated ferrets. Most of the ferrets caged with the inoculated animals showed evidence of viral shedding and had H9 antibodies.

    The authors write that the results suggest H9N2 infections in ferrets are similar to those in humans and pigs. "Our findings suggest that the ferret represents a good animal model to study the potential changes that could lead to efficient transmission of avian H9N2 viruses in humans," they state.

    Next, they investigated whether one of the H9N2 viruses they used could be transmitted by aerosol to ferrets. Though the virus was found in the inoculated and direct-contact ferrets, they found no seroconversion in ferrets that were kept separate but shared the same air as the other animals. "Taken together, these data indicate that although some H9N2 viruses can transmit to direct contacts, they lack successful aerosol transmission," the report says.

    The study also explored genetic-level aspects of H9N2 transmission in ferrets. For example, they found that:

    A single change of glycine (Gln) to leucine (Leu) at amino acid position 226 in the hemagglutinin receptor binding site enhanced H9N2 replication
    Leucine residue at position 226 of the hemagglutinin receptor binding site appears to select for human virus–like receptor specificity that enhances replication and direct contact transmission.

    Another goal was to determine if an H9N2 avian-human reassortment would enhance transmission of H9N2 strains that contained Leu226. Using reverse genetics, they recovered a reassortant that combined surface protein genes from H9N2 with internal genes from an H3N2 virus. Ferrets that were inoculated with the virus, as well as their direct contacts, had high H9 antibody titers, but the aerosol contacts did not.

    The authors report that the reassortant virus showed enhanced shedding and transmission, but it lacked the ability to infect aerosol contacts. The reassortant also caused more severe damage in the lungs, replicating in both the upper and lower respiratory tracts, than a wild-type H9N2 virus.

    The group concluded that H9N2 viruses are poised for further adaptation that could make transmission more efficient among mammals and humans. Though they did not find aerosol transmission, a key feature of a pandemic influenza strain, an abundance of other risk factors, such as the human virus-like specificity in some avian and swine isolates, build a strong case for H9N2 as a potential public health threat , they assert.

    Wan H, Sorrell EM, Song H, et al. Replication and transmission of H9N2 influenza viruses in ferrets: evaluation of pandemic potential. PLoS One 2008 Aug;3(8):1-13 [Full text]

    See also:

    Mar 20, 2007, CIDRAP News story "Baby in Hong Kong infected with H9N2 avian flu"

    Researchers probe pandemic potential of H9N2 virus
    http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/aug1408avian-br2.html
    ?Addressing chronic disease is an issue of human rights ? that must be our call to arms"
    Richard Horton, Editor-in-Chief The Lancet

    ~~~~ Twitter:@GertvanderHoek ~~~ GertvanderHoek@gmail.com ~~~

    Comment

    • #3
      Re: Swine H9N2 - pandemic potential?

      Slide 10 of the above referenced powerpoint shows humans cases of H9N2:


      H9N2 LPAI - China - ?98,?99 - 5 cases

      H9N2 LPAI - Hong Kong - ?97, ?03, ?07 - 4 cases

      .
      "The next major advancement in the health of American people will be determined by what the individual is willing to do for himself"-- John Knowles, Former President of the Rockefeller Foundation

      Comment

      • #4
        Re: Swine H9N2 - pandemic potential?

        From Vietnam
        Translation Vietnamese-English

        Influenza A/H9N2 virus is very dangerous

        Updated at 16h17, on September 17, 2009 --

        While influenza A/H1N1 services are spread across the continents, the scientists warn other line influenza A virus, H9N2 has the symbol similar to the risk of avian influenza virus H5N1. Experimental H9N2 line shows only a slight change also has a pathogenic virus H5N1 is not bad.

        A few years ago in Hong Kong, scientists have isolated the H9N2 virus in patients of 4 products patients, although these viruses are mainly in poultry, pigs and other animals in Europe and Asia.

        Research Published in the journal Public Library of Science, scientist Daniel Perez and colleagues at the University of Maryland, the U.S. has tested H9N2 virus in ferret dew - there species biological response similar to previous flu response response of.

        Only a variation also makes H9N2 becomes more toxic, and make it easy to infection from the weasels to the options. They also try to combine H9N2 with H3N2, influenza virus is common in people, creating a virus mixture. Results showed that weasels frost susceptible and contagious virus mixture.


        404 Not Found
        http://vnmedia.vn/newsdetail.asp?CatId=73&NewsId=174638
        "Safety and security don't just happen, they are the result of collective consensus and public investment. We owe our children, the most vulnerable citizens in our society, a life free of violence and fear."
        -Nelson Mandela

        Comment

        • #5
          Re: Swine H9N2 - pandemic potential?

          H9N2 also adds increased genetical material to reassort with.
          H5N1 already demonstrated in birds that it likes to reassort
          with H9N2.

          Now these viruses enter pigs on a regular base and maybe
          are starting to go back to birds and mix with bird viruses
          for a greatly enhanced evolution of flu in pigs.

          Without avian flu going to European pigs in 1978
          we would have no ****** now.
          Same for the <1998 jump in America.
          These avian genes enhance their chances
          to establish in other species by reassortment events.
          I'm interested in expert panflu damage estimates
          my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

          Comment

          • #6
            Re: Swine H9N2 - pandemic potential?

            Originally posted by gsgs View Post
            .......
            Now these viruses enter pigs on a regular base and maybe
            are starting to go back to birds and mix with bird viruses
            for a greatly enhanced evolution of flu in pigs.

            Without avian flu going to European pigs in 1978
            we would have no ****** now.
            Same for the <1998 jump in America.
            These avian genes enhance their chances
            to establish in other species by reassortment events.
            all years of swine H9N2 in NCBI database:


            ABL61414 554 Swine HA H9N2 China 2003 Influenza A virus(A/swine/Shandong/fLS/2003(H9N2))
            ABL61432 522 Swine HA H9N2 China 2003 Influenza A virus(A/swine/Shandong/fJN/2003(H9N2))
            ABK00143 540 Swine HA H9N2 China 2003 Influenza A virus (A/swine/Shandong/na/2003(H9N2))
            ABL61468 522 Swine HA H9N2 China 2003 Influenza A virus(A/swine/Shandong/fNY/2003(H9N2))
            ACA42418 560 Swine HA H9N2 China 2003 Influenza A virus (A/swine/Shandong/w4/2003(H9N2))
            ABL61504 524 Swine HA H9N2 China 2003 Influenza A virus(A/swine/Shandong/fHZ/2003(H9N2))
            ABL61495 522 Swine HA H9N2 China 2003 Influenza A virus(A/swine/Shandong/fZC/2003(H9N2))
            AAP47821 560 Swine HA H9N2 China 2003 Influenza A virus (A/Sw/ShanDong/1/2003(H9N2))
            ABL61477 552 Swine HA H9N2 China 2004 Influenza A virus(A/swine/Henan/7/2004(H9N2))
            ACA42428 560 Swine HA H9N2 China 2004 Influenza A virus (A/swine/Guangdong/wxl/2004(H9N2))
            ABL61441 532 Swine HA H9N2 China 2004 Influenza A virus(A/swine/Henan/8/2004(H9N2))
            ABL61450 545 Swine HA H9N2 China 2004 Influenza A virus(A/swine/Henan/5/2004(H9N2))
            ACA25348 560 Swine HA H9N2 China 2004 Influenza A virus (A/swine/Jiangxi/1/2004(H9N2))
            ACA25358 560 Swine HA H9N2 China 2004 Influenza A virus (A/swine/Jiangxi/wx2/2004(H9N2))
            ABL61405 542 Swine HA H9N2 China 2004 Influenza A virus(A/swine/Henan/3/2004(H9N2))
            ABL61459 552 Swine HA H9N2 China 2004 Influenza A virus(A/swine/Henan/4/2004(H9N2))
            ABL61486 552 Swine HA H9N2 China 2004 Influenza A virus(A/swine/Henan/2/2004(H9N2))
            ABL61423 555 Swine HA H9N2 China 2004 Influenza A virus(A/swine/Henan/6/2004(H9N2))
            ABQ51935 560 Swine HA H9N2 China 2005 Influenza A virus (A/swine/Guangxi/58/2005(H9N2))
            ABI96715 532 Swine HA H9N2 China 2005 Influenza A virus (A/swine/Shandong/nc/2005(H9N2))
            ABV31959 560 Swine HA H9N2 China 2005 Influenza A virus (A/swine/Guangxi/S15/2005(H9N2))
            ABV31939 560 Swine HA H9N2 China 2005 Influenza A virus (A/swine/Guangxi/FS2/2005(H9N2))
            ABV31960 560 Swine HA H9N2 China 2005 Influenza A virus (A/swine/Guangxi/S11/2005(H9N2))
            BAB85617 320 Swine HA H9N2 Hong Kong 1998 Influenza A virus (A/swine/Hong Kong/10/98(H9N2))
            AAL14081 550 Swine HA H9N2 Hong Kong 1998 Influenza A virus (A/swine/Hong Kong/10/98(H9N2))
            AAL14080 550 Swine HA H9N2 Hong Kong 1998 Influenza A virus (A/swine/Hong Kong/9/98(H9N2))
            BAB85618 320 Swine HA H9N2 Hong Kong 1998 Influenza A virus (A/swine/Hong Kong/9/98(H9N2))
            AAL30486 336 Swine HA H9N2 Hong Kong 1998 Influenza A virus (A/swine/Hong Kong/2106/98(H9N2))
            AAL30487 336 Swine HA H9N2 Hong Kong 1998 Influenza A virus (A/swine/Hong Kong/3297/98(H9N2))
            AAV68022 560 Swine HA H9N2 South Korea 2004 Influenza A virus (A/swine/Korea/S452/2004(H9N2))
            AAV68014 368 Swine HA H9N2 South Korea 2004 Influenza A virus (A/swine/Korea/S190/2004(H9N2))
            .
            "The next major advancement in the health of American people will be determined by what the individual is willing to do for himself"-- John Knowles, Former President of the Rockefeller Foundation

            Comment

            • #7
              Re: Swine H9N2 - pandemic potential?

              recent (2008 and 2009) H9N2 in birds:

              ACG59782 354 Avian HA H9N2 China 2008 Influenza A virus (A/chicken/Henan/L2/2008(H9N2))
              ACJ35235 560 Avian HA H9N2 China 2008/05 Influenza A virus (A/chicken/Anhui/AH16/2008(H9N2))
              ACJ35239 560 Avian HA H9N2 China 2008/05 Influenza A virus (A/chicken/Anhui/AK25/2008(H9N2))
              ACT36339 295 Avian HA H9N2 China 2008 Influenza A virus (A/chicken/Shanghai/Y2/2008(H9N2))
              ACG59781 353 Avian HA H9N2 China 2008 Influenza A virus (A/chicken/Henan/L1/2008(H9N2))
              ACJ35237 560 Avian HA H9N2 China 2008/05 Influenza A virus (A/chicken/Anhui/AI16/2008(H9N2))
              ACL11939 354 Avian HA H9N2 China 2008 Influenza A virus (A/chicken/Henan/L3/2008(H9N2))
              ACT36336 295 Avian HA H9N2 China 2008 Influenza A virus (A/chicken/Shanghai/Y1/2008(H9N2))
              ACF93487 560 Avian HA H9N2 China 2008 Influenza A virus (A/chicken/Guangdong/GZ02/2008(H9N2))
              ACH95472 560 Avian HA H9N2 China 2008/03/16 Influenza A virus (A/chicken/Shandong/lx316/2008(H9N2))
              ACG59779 354 Avian HA H9N2 China 2008 Influenza A virus (A/chicken/Zibo/L2/2008(H9N2))
              ACG59780 354 Avian HA H9N2 China 2008 Influenza A virus (A/chicken/Zibo/B1/2008(H9N2))
              ACJ35236 560 Avian HA H9N2 China 2008/05 Influenza A virus (A/chicken/Anhui/AH23/2008(H9N2))
              ACJ35238 560 Avian HA H9N2 China 2008/05 Influenza A virus (A/chicken/Anhui/AK13/2008(H9N2))
              ACN58060 560 Avian HA H9N2 Iran 2008/12 Influenza A virus (A/chicken/Iran/SS2/2008(H9N2))
              ACR48904 560 Avian HA H9N2 Israel 2008/06/10 Influenza A virus (A/chicken/Israel/182/2008(H9N2))
              ACR48905 560 Avian HA H9N2 Israel 2009/02/15 Influenza A virus (A/chicken/Israel/184/2009(H9N2))
              ACR48910 560 Avian HA H9N2 Israel 2008/04/18 Influenza A virus (A/chicken/Israel/694/2008(H9N2))
              ACR48903 560 Avian HA H9N2 Israel 2008/06/01 Influenza A virus (A/chicken/Israel/54/2008(H9N2))
              ACR48911 560 Avian HA H9N2 Israel 2008/04/21 Influenza A virus (A/chicken/Israel/702/2008(H9N2))
              ACJ68653 560 Avian HA H9N2 Israel 2008/01/25 Influenza A virus (A/chicken/Israel/292/2008(H9N2))
              ACR48906 560 Avian HA H9N2 Israel 2008/06/27 Influenza A virus (A/chicken/Israel/310/2008(H9N2))
              ACR48907 560 Avian HA H9N2 Israel 2008/06/29 Influenza A virus (A/chicken/Israel/330/2008(H9N2))
              ACR48909 560 Avian HA H9N2 Israel 2008/04/15 Influenza A virus (A/turkey/Israel/689/2008(H9N2))
              ACR48913 560 Avian HA H9N2 Israel 2008/06/13 Influenza A virus (A/chicken/Israel/883/2008(H9N2))
              ACJ68664 560 Avian HA H9N2 Israel 2008 Influenza A virus (A/avian/Israel/313/2008(H9N2))
              ACJ68675 560 Avian HA H9N2 Israel 2008 Influenza A virus (A/avian/Israel/314/2008(H9N2))
              ACJ68719 560 Avian HA H9N2 Israel 2008/03/09 Influenza A virus (A/chicken/Israel/524/2008(H9N2))
              BAH23432 560 Avian HA H9N2 Japan 2008 Influenza A virus (A/duck/Hokkaido/238/2008(H9N2))
              ACP50730 560 Avian HA H9N2 Pakistan 2008/03/04 Influenza A virus (A/chicken/Pakistan/UDL-03/2008(H9N2))
              ACP50708 560 Avian HA H9N2 Pakistan 2008/01/09 Influenza A virus (A/chicken/Pakistan/UDL-01/2008(H9N2))
              ACP50719 560 Avian HA H9N2 Pakistan 2008/02/22 Influenza A virus (A/chicken/Pakistan/UDL-02/2008(H9N2))
              .
              "The next major advancement in the health of American people will be determined by what the individual is willing to do for himself"-- John Knowles, Former President of the Rockefeller Foundation

              Comment

              • #8
                Re: Swine H9N2 - pandemic potential?

                all years of human H9N2 in NCBI database:

                AAL32476 496 Human HA H9N2 China 1998 Influenza A virus (A/Shantou/239/98(H9N2))
                AAL32477 496 Human HA H9N2 China 1998 Influenza A virus (A/Shaoguan/408/98(H9N2))
                AAL32478 496 Human HA H9N2 China 1998 Influenza A virus (A/Shaoguan/447/98(H9N2))
                AAL32479 496 Human HA H9N2 China 1999 Influenza A virus (A/Guangzhou/333/99(H9N2))
                CAB95857 560 Human HA H9N2 Hong Kong 1999 Influenza A virus (A/Hong Kong/1074/99(H9N2))
                BAB85616 320 Human HA H9N2 Hong Kong 1999 Influenza A virus (A/Hong Kong/1073/99(H9N2))
                CAB95856 560 Human HA H9N2 Hong Kong 1999 Influenza A virus (A/Hong Kong/1073/99(H9N2))
                ABB58945 525 Human HA H9N2 Hong Kong 2003 Influenza A virus (A/HK/2108/2003(H9N2))
                .
                "The next major advancement in the health of American people will be determined by what the individual is willing to do for himself"-- John Knowles, Former President of the Rockefeller Foundation

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