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H5N1: Mutations described as typical of human influenza viruses found in Africa

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  • H5N1: Mutations described as typical of human influenza viruses found in Africa

    Highly Pathogenic Avian Influenza Virus Subtype H5N1 in Africa: A Comprehensive Phylogenetic Analysis and Molecular Characterization of Isolates

    Giovanni Cattoli and others

    Abstract

    Highly pathogenic avian influenza virus A/H5N1 was first officially reported in Africa in early 2006. Since the first outbreak in Nigeria, this virus spread rapidly to other African countries. From its emergence to early 2008, 11 African countries experienced A/H5N1 outbreaks in poultry and human cases were also reported in three of these countries.

    At present, little is known of the epidemiology and molecular evolution of A/H5N1 viruses in Africa. We have generated 494 full gene sequences from 67 African isolates and applied molecular analysis tools to a total of 1,152 A/H5N1 sequences obtained from viruses isolated in Africa, Europe and the Middle East between 2006 and early 2008.

    Detailed phylogenetic analyses of the 8 gene viral segments confirmed that 3 distinct sublineages were introduced, which have persisted and spread across the continent over this 2-year period. Additionally, our molecular epidemiological studies highlighted the association between genetic clustering and area of origin in a majority of cases.

    Molecular signatures unique to strains isolated in selected areas also gave us a clearer picture of the spread of A/H5N1 viruses across the continent.

    Mutations described as typical of human influenza viruses in the genes coding for internal proteins or associated with host adaptation and increased resistance to antiviral drugs have also been detected in the genes coding for transmembrane proteins.

    These findings raise concern for the possible human health risk presented by viruses with these genetic properties and highlight the need for increased efforts to monitor the evolution of A/H5N1 viruses across the African continent.

    They further stress how imperative it is to implement sustainable control strategies to improve animal and public health at a global level.

    More:

    http://www.plosone.org/article/info%...l.pone.0004842
    “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 ~~~

  • #2
    Re: H5N1: Mutations described as typical of human influenza viruses found in Africa

    Yes. I posted a summary in scientific library, and African viruses were found to contain several changes in NS1 segment (similar to 1918 virus, KSEV, instead to human flu RSKV), PB2, etc.

    Comment


    • #3
      Re: H5N1: Mutations described as typical of human influenza viruses found in Africa

      Another linked study: http://www.flutrackers.com/forum/sho...37&postcount=1

      Comment


      • #4
        Re: H5N1: Mutations described as typical of human influenza viruses found in Africa

        About NS1 and human/avian signatures (KSEV, RSEV, RSKV etc.):

        A new influenza virus virulence determinant: The NS1 protein four C-terminal residues modulate pathogenicity

        David Jackson,* Md. Jaber Hossain,† Danielle Hickman,† Daniel R. Perez,† and Robert A. Lamb*‡
        *Howard Hughes Medical Institute and Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, IL 60208; and
        †Department of Veterinary Medicine, University of Maryland, College Park, MD 20742
        ‡To whom correspondence should be addressed. E-mail: ralamb@northwestern.edu
        Contributed by Robert A. Lamb, January 17, 2008.
        Author contributions: D.J., M.J.H., D.R.P., and R.A.L. designed research; D.J., M.J.H., and D.H. performed research; D.J., M.J.H., D.H., D.R.P., and R.A.L. analyzed data; and D.J., D.R.P., and R.A.L. wrote the paper.
        Received December 18, 2007.
        Freely available online through the PNAS open access option.
        Small right arrow pointing to: This article has been cited by other articles in PMC.


        Abstract

        The virulence of influenza virus is a multigenic trait. One determinant of virulence is the multifunctional NS1 protein that functions in several ways to defeat the cellular innate immune response.

        Recent large-scale genome sequence analysis of avian influenza virus isolates indicated that four C-terminal residues of the NS1 protein is a PDZ ligand domain of the X-S/T-X-V type and it was speculated that it may represent a virulence determinant.

        To test this hypothesis, by using mice as a model system, the four C-terminal amino acid residues of a number of influenza virus strains were engineered into the A/WSN/33 virus NS1 protein by reverse genetics and the pathogenicity of the viruses determined.

        Viruses containing NS1 sequences from the 1918 H1N1 and H5N1 highly pathogenic avian influenza (HPAI) viruses demonstrated increased virulence in infected mice compared with wt A/WSN/33 virus, as characterized by rapid loss of body weight, decreased survival time, and decreased mean lethal dose.

        Histopathological analysis of infected mouse lung tissues demonstrated severe alveolitis, hemorrhaging, and spread of the virus throughout the entire lung.

        The increase in pathogenicity was not caused by the overproduction of IFN, suggesting the NS1 protein C terminus may interact with PDZ-binding protein(s) and modulate pathogenicity through alternative mechanisms.

        Keywords: mouse model for influenza, PDZ domains, PDZ ligand, influenza reverse genetics, H5N1 influenza
        -
        http://www.pubmedcentral.nih.gov/art...tool=pmcentrez
        -----

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        • #5
          Re: H5N1: Mutations described as typical of human influenza viruses found in Africa

          From above paper:


          <table style="width: auto;"><tbody><tr><td></td></tr><tr><td style="font-family: arial,sans-serif; font-size: 11px; text-align: right;">From TABLES</td></tr></tbody></table>

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          • #6
            Re: H5N1: Mutations described as typical of human influenza viruses found in Africa

            From its emergence to early 2008, 11 African countries experienced A/H5N1 outbreaks in poultry and human cases were also reported in three of these countries.
            Human cases have been reported from Egypt, Nigeria, and Djibouti. The other eight countries with poultry infections, as noted in the article referenced in post 1, are Benin, Burkina Faso, Cameroon, Ghana, Ivory Coast, Niger, Sudan, and Togo. the map below shows the location of these 11 countries in the continent of Africa.

            Name:  1531fa8bbe9516d102ffaf2787a39c0d.jpg
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            http://novel-infectious-diseases.blogspot.com/

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