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Resolved: Why bird flu virus is not contagious between humans

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  • Resolved: Why bird flu virus is not contagious between humans

    Resolved: Why bird flu virus is not contagious between humans

    PARIS - Virologists say they understand why bird influenza in its present form does not spread among humans, and the finding suggests the world may have a precious breathing space to prepare for any flu pandemic.

    The reason lies in minute differences to cells located in the top and bottom of the airways, the team report in Thursday's issue of Nature, the weekly British science journal.

    To penetrate a cell, the spikes that stud an influenza virus have to be able to bind to the cellular surface.

    The virus spike is like a key and the cell's docking point, called a receptor, is like a lock. They both have to be the right shape for the connection to happen.

    Scientists in the United States and Japan, led by Yoshihiro Kawaoka of the
    University of Wisconsin at Madison, found that avian influenza viruses and human influenza viruses home in on slightly different receptors.

    The receptor preferred by human flu is more prevalent in cells in the mucous lining of the nose and sinus as well as the throat, trachea and bronchi.

    But the receptor preferred by bird flu tends to be found among cells deep in the lung, in ball-like structures called the alveoli.

    It means H5N1 is likely to hole up in a part of the airways that does not cause coughing and sneezing -- the means by which the flu virus is classically transmitted among humans.

    Bird flu is lethal to poultry and dangerous for humans in close proximity to infected fowl. It has claimed more than 100 lives, according to a World Health Organisation (WHO) toll.

    But, apart from a few anecdotal cases, the mortality has occurred exclusively by direct transmission from birds to humans and not among humans themselves. To acquire that contagiousness would open the way to a pandemic.

    "Our findings indicate that H5N1 virus... can replicate efficiently only in cells in the lower region of the respiratory tract, where the avian virus receptor is prevalent," the paper says.

    "This restriction may contribute to the inefficient human-to-human transmission of H5N1 viruses seen to date."

    So what would turn H5N1 into a pandemic virus?

    First and foremost, it would need mutations in the spike, the haemagglutinin (HA) molecule, to enable the virus to bind to cells in the upper respiratory tract.

    This would enable the virus to spread via coughs and sneezes and nasal mucus, which are caused by irritation to the upper airways.

    To boost its pandemic potential, the virus also needs changes in its PB2 gene, which controls an enzyme essential for efficient reproduction.

    "Nobody knows whether the virus will evolve into a pandemic strain, but flu viruses constantly change," said Kawaoka.

    "Certainly, multiple mutations need to be accumulated for the H5N1 to become a pandemic strain."

    The findings suggest scientists and public health agencies may have more time to prepare for an eventual pandemic of avian influenza, the team believe.

    Kawaoka's team exposed various tissues from the human respiratory tract to a range of viruses in lab dishes.

    The viruses were the human strains H1N1 and H3N2 and the bird strains H3N2 and H4N6. In addition, there were two H5N1 samples, one taken from a human victim in Hong Kong and one from a duck in Vietnam.

    Flu viruses reproduce sloppily, which induces slight changes in their genetic code. This movement is called antigenic drift, and explains why seasonal flu viruses keep changing and new updated vaccines are needed.

    But they can also make big changes, called antigenic shift, in which new genes are brought in, thus creating a new pathogen against which no one has immunity. A novel flu virus that emerged after World War I killed as many as 50 million people.

    By closely monitoring viruses from people infected with avian flu, scientists can get an early warning as to whether these strains are mutating into forms that will make it easier to fit into human receptors, Kawaoka said. - AFP/ir

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  • #2
    Bird Flu Infects Body in Wrong Place to Spread Easily, Studies Say



    Bird Flu Infects Body in Wrong Place to Spread Easily, Studies Say

    NEW YORK (AP) -- Scientists say they've found a reason bird flu isn't spreading easily from person to person: The virus concentrates itself too deep in the respiratory tract to be spewed out by coughing and sneezing.

    But the virus could change that behavior by genetic mutation, taking a step toward unleashing a worldwide outbreak of lethal flu.

    Experts said the new finding doesn't indicate how likely such a pandemic is. The virus may also need other mutations to take off in the human population, they said. Still, the work suggests a particular sign to watch for in new virus samples to help gauge the danger to humans.

    The work, reported in Thursday's issue of the journal Nature, comes from University of Wisconsin-Madison virologist Yoshihiro Kawaoka with colleagues in Japan. Similar results, from the Erasmus Medical Center in Rotterdam, the Netherlands, will be published online Thursday by the journal Science.

    More than 180 people are known to have been infected with the bird flu virus H5N1. Virtually all are believed to have caught it from infected poultry. But scientists have long warned that the virus, which is prone to mutation, could transform itself into a version that spreads easily from person to person. That germ could touch off a pandemic.

    Ordinary flu viruses spread when an infected person coughs or sneezes, blasting out tiny droplets carrying the germ to others. For that to happen, the virus has to be perched in the right places to be ejected by a cough or sneeze. The new work suggests H5N1, by contrast, infects humans too low in the respiratory tract for that to occur.

    Both research teams used human tissue removed from various parts of the respiratory tract - the region from the nose to the lung - to study where virus infection occurs.

    Scientists already knew that bird flu viruses use a specific kind of docking site to enter cells they infect, while human flu viruses use a different one. Kawaoka's group found the bird virus docking site appears mostly on lung cells, while being rare on cells found in higher areas like the nose and windpipe. Those higher areas were dominated instead by the human-type docking site.

    Kawaoka said that for H5N1 to become a pandemic virus, it would have to mutate in a way that lets it attach to the same docking site human viruses use. Other mutations would be needed as well, he said in a statement.

    Robert M. Krug of the University of Texas at Austin called Kawaoka's work an important observation, and said that if H5N1 begins to use the human virus docking site ``we've got a lot to worry about.'' It's not clear whether that would be enough to produce a pandemic germ, he said.

    James Paulson of the Scripps Research Institute in La Jolla, Calif., stressed that other viral factors may be important in human-to-human transmission. But he said that once the virus has a foothold in a person, regardless of where it is in the respiratory tract, it may mutate to gain the abilities it needs to start spreading among people.

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    • #3
      Re: Resolved: Why bird flu virus is not contagious between humans

      Resolved... they think that will change reality regarding how the virus changes???

      There's not too much new in this study except to come at the species barrier hypothesis from another direction. Science published the seminal work on docking site affinities, as these articles acknowledge...

      Scientists already knew that bird flu viruses use a specific kind of docking site to enter cells they infect, while human flu viruses use a different one. Kawaoka's group found the bird virus docking site appears mostly on lung cells, while being rare on cells found in higher areas like the nose and windpipe. Those higher areas were dominated instead by the human-type docking site.
      So long as the changes in the H5N1 genome are believed to occur by RANDOM mutation to the HA docking sites, virologists and the public are likely to be lulled into thinking this pandemic is likely not to come for a while, if ever...

      To them I would say "Watch what the virus has done and is doing..." It's on the move, going epizootic, expanding both geographical reach and species involvement."

      Dr Niman, keep publicizing info on the sequences as they're released...

      Recombination.... paradigm shift....

      Wildland firefighter saying: Prepare for the worst; expect the best...
      LCES: Lookouts, Communications, Escape Routes, Safety Zones
      Mellie saying: Enjoy your life!
      Old Chinese Blessing: May you live in interesting times...

      Comment


      • #4
        Re: Resolved: Why bird flu virus is not contagious between humans

        Old Chinese Blessing: May you live in interesting times...

        I thought that was an old chinese curse.

        Comment


        • #5
          Re: Resolved: Why bird flu virus is not contagious between humans

          Only for those who are not alert to paradigm shifts!

          Comment


          • #6
            S227N H5N1 In Human Upper and Lower Respiratory Tract

            S227N H5N1 In Human Upper and Lower Respiratory Tract

            <table style="width: 775px; text-align: left; color: rgb(190, 5, 1); font-family: helvetica,arial,sans-serif;" border="0" cellpadding="0" cellspacing="0"> <tbody><tr><td colspan="5" style="vertical-align: top; width: 515px;">Recombinomics Commentary
            March 22, 2006

            It is interesting that the A/Hong Kong/213/03 (H5N1) virus, which was isolated from a human and recognizes both SA2,3Gal and SA2,6Gal (ref. 6), bound extensively to both bronchial and alveolar cells.

            The above comments in tomorrow?s Nature may explain the large cluster in Turkey associated with S227N detected in the index case. S227N had previously been shown to have reduced affinity for avian receptors (SA2,3Gal) and increased affinity for human receptors (SA2.6Gal). Although the recent paper in Science failed to find increased affinity for SA2,6Gal, the S227N was on a genetic background from an isolate in Vietnam which was distinct from the Hong Kong isolate listed above. In Turkey, the S227N was on a Qinghai strain background, which is different than both the Vietnam or Hong Kong strains used in the lab experiments.

            However, the size of the cluster in Turkey suggests that H5N1 was more efficiently transmitted human-to-human, which would be consistent with increased affinity for SA2.6Gal receptors. The H5N1 from the index case was said to be a mixture of S227N and wild type S227. Only wild type was detected in the sister of the index case, in contrast to the Hong Kong isolates which had S227N from both the father and son. However, the Hong Kong isolates were grown on a canine cell line, MDCK, as was the H5N1 used in the Nature paper. It is unclear what was used to isolate H5N1 from the index case and his sister. Isolation of H5N1 on chicken eggs can reduce or eliminate S227N.

            However, changes in the levels of S227N and wild type could have been modulated in the patients. H5N1 was isolated from lung tissue, which may have selected against S227N in vivo, since the above data suggests the wild type would grow more efficiently in lung tissue.

            Thus, the S227N could have facilitated growth in the upper respiratory tract, while S227 could have been more involved in growth in the lower respiratory tract. Genes encoding S227 could have entered the upper respiratory tract in a pseudo-typed H5N1.

            These data could also explain the cluster of cases in Azerbaijan which were fatal, yet efficient transmitted between the index case, her two cousins, and a close friend.

            More sequence information on the Azerbaijan cluster would be useful.

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            </td> <td style="vertical-align: top; width: 170px; background-color: rgb(255, 255, 255);">http://www.recombinomics.com/News/03...per_Lower.html</td></tr></tbody> </table>

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