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Cell. Identification, Characterization, and Natural Selection of Mutations Driving Airborne Transmission of A/H5N1 Virus

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  • Cell. Identification, Characterization, and Natural Selection of Mutations Driving Airborne Transmission of A/H5N1 Virus

    [Source: Cell, full page: (LINK). Abstract, edited.]

    Article

    Identification, Characterization, and Natural Selection of Mutations Driving Airborne Transmission of A/H5N1 Virus

    Martin Linster, Sander van Boheemen, Miranda de Graaf, Eefje J.A. Schrauwen, Pascal Lexmond, Benjamin M?nz, Theo M. Bestebroer, Jan Baumann, Debby van Riel, Guus F. Rimmelzwaan, Albert D.M.E. Osterhaus, Mikhail Matrosovich, Ron A.M. Fouchier, Sander Herfst

    Published: April 10, 2014

    DOI: http://dx.doi.org/10.1016/j.cell.2014.02.040


    Highlights
    • Five substitutions are sufficient for airborne transmission of A/H5N1 between ferrets
    • Two substitutions in PB1 and PB2 increased RNA transcription and virus replication
    • Three HA substitutions altered receptor binding preference and lowered pH of fusion
    • Strong selective advantage of substitutions responsible for airborne transmission


    Summary

    Recently, A/H5N1 influenza viruses were shown to acquire airborne transmissibility between ferrets upon targeted mutagenesis and virus passage. The critical genetic changes in airborne A/Indonesia/5/05 were not yet identified. Here, five substitutions proved to be sufficient to determine this airborne transmission phenotype. Substitutions in PB1 and PB2 collectively caused enhanced transcription and virus replication. One substitution increased HA thermostability and lowered the pH of membrane fusion. Two substitutions independently changed HA binding preference from α2,3-linked to α2,6-linked sialic acid receptors. The loss of a glycosylation site in HA enhanced overall binding to receptors. The acquired substitutions emerged early during ferret passage as minor variants and became dominant rapidly. Identification of substitutions that are essential for airborne transmission of avian influenza viruses between ferrets and their associated phenotypes advances our fundamental understanding of virus transmission and will increase the value of future surveillance programs and public health risk assessments.


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  • #2
    Re: Cell. Identification, Characterization, and Natural Selection of Mutations Driving Airborne Transmission of A/H5N1 Virus

    [Source: NPR, full page: (LINK).]


    Scientists Publish Recipe For Making Bird Flu More Contagious

    Researchers ignited a debate three years ago when they changed a deadly flu virus so that it could spread between people. Only five mutations are needed to turn the virus into a pandemic threat.

    (?)


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    Comment


    • #3
      Re: Cell. Identification, Characterization, and Natural Selection of Mutations Driving Airborne Transmission of A/H5N1 Virus

      Updated: April 10, 2014 | 5:28 pm Adjust Text Size
      Five mutations could send bird flu virus airborne : Study
      By Helen Branswell

      snip

      ?We now have intentionally lowered the bar to the point ? where we have made it possible for laboratories around the world to do this work,? said Osterholm, who is the director of the Center for Infectious Diseases Research and Policy at the University of Minnesota.

      ?I think what remains very problematic is just the enabling information it provides. There are a lot of laboratories around the world that are not funded by the U.S. government, do not have specific restrictions or limitations on what they can do relative to biosafety.?

      more..

      Comment


      • #4
        Re: Cell. Identification, Characterization, and Natural Selection of Mutations Driving Airborne Transmission of A/H5N1 Virus

        Undoubtedly, bio-hazards reduction policies have to be enhanced after these publications, in order to protect public health at global level.

        Recent nerve gas use in Syria would have suggested more restraint in some researchers activities, because around the world there are many criminals (at any level) able to purchase, fund, and develop mass-destruction bio-chemical-weapons.

        Since some other research and policy Group are suggesting to cut pandemic preparedness antivirals stockpiling, citing a supposed overhype in the alleged effectiveness of the drugs and the pumped risk assessment of certain viruses with pandemic potential for profitable use, we are preparing the global community for a perfect storm: engineered pathogens able to cause explosive outbreaks if deliberately or mistakenly released into the human population, unregulated research in potential bio-hazardous methods, decreased interest in pandemic preparedness and cuts in related public expenditures, disabled first line drugs arsenal: well all these things will contribute to cause unpredictable scenarios in the future.

        We are seeing the impact on a severely impoverished population in West Africa of an untreatable condition (EVD), where both the dilapidated health infrastructure, and lack of the minimal medical countermeasure are working together in destroying the life of thousands of people, either ill or affected by the economic impact of disease.

        More restraint is clearly needed as well as a correct enhancement of bio-safety policy at all levels.

        GM

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        • #5
          Re: Cell. Identification, Characterization, and Natural Selection of Mutations Driving Airborne Transmission of A/H5N1 Virus

          Source: http://www.latimes.com/science/scien...,6818032.story

          Deadly H5N1 bird flu needs just 5 mutations to spread easily in people
          By Monte Morin This post has been updated, as indicated below.
          April 10, 2014, 3:14 p.m.

          It?s a flu virus so deadly that scientists once halted research on the disease because governments feared it might be used by terrorists to stage a biological attack.

          Yet despite the fact that the H5N1 avian influenza has killed 60% of the 650 humans known to be infected since it was identified in Hong Kong 17 years ago, the ?bird flu? virus has yet to evolve a means of spreading easily among people.

          Now Dutch researchers have found that the virus needs only five favorable gene mutations to become transmissible through coughing or sneezing, like regular flu viruses.

          World health officials have long feared that the H5N1 virus will someday evolve a knack for airborne transmission, setting off a devastating pandemic. While the new study suggests the mutations needed are relatively few, it remains unclear whether they?re likely to happen outside the laboratory...

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