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A list of relevant mutation position

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  • #31
    Re: A list of relevant mutation position

    The two isolates from Hunan, A/chicken/Hunan/2246/2006(H5N1) and A/chicken/Hunan/2292/2006(H5N1). which had two of the same changes in Shanxi, T192I and L194I, also had two additional changes, D187N and A189E.

    These are partial sequences, but have all of the receptor binding domain. The sequence goes through the HA cleavage site.
    Last edited by AlaskaDenise; November 12, 2006, 05:09 AM.

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    • #32
      Re: A list of relevant mutation position

      "count" is the number of sequences at genbank with that
      particular pattern of amino-acids at those 35 positions near to the RBD.
      I'm interested in expert panflu damage estimates
      my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

      Comment


      • #33
        Re: A list of relevant mutation position

        My simple question to gsgs is "Do you agree with the facts stated below?" This is a yes or no answer, with an explanation as to which points you differ and wish to add commentary here.

        As a follow on question, "Do you expect there to be more polymorphism changes in the near term based on the fact that both the cleavage and receptor sites now, this year, are showing previously unrecognized changes? If yes, do you have a formula for the rate or the direction of those changes? If no, why not?

        To help you gsgs in your response, as I do wish for you to get an answer based on facts, not skewed so heavily towards inquisitive thinking alone, here's what Niman just posted elsewhere on the internet,

        > The Shanxi sequence, with the multiple changes in or near the receptor binding domain and the acquisition of mammalian polymorphisms in PB1 and MP was isolated in 2006, as were the two related sequences from Hunan and the five Shantou sequences.

        > The large number of changes in an around the receptor binding domain of an H5N1 isolate is without precedent, so a year ago there were ZERO such sequences reported.

        > The story is in the sequence, and it is becoming increasingly easy to read. <

        Yet, I will agree with you that it's possible that one year ago, the virologists sequencing weren't looking that closesly at receptor binding domains as they are now, and thus the changes being seen are no different than the changes that occur each year. That's to be further explained, maybe by you?

        Originally posted by niman
        Here are a few comments to put the above table in perspective. Most attention is focused on H5N1 because it has a polybasic HA cleavage site and has caused virtually all reported human fatalities from avian influenza. The common cleavage site, first described in 1996 is undergoing rapid change, especially in 2005 and 2006. In fact each major strain of H5N1 causing human fatalities has a different cleavage site. Clade 1 in southeast Asia has the original site, QRERRRKKR. The Qinghai stain, killing people in Turkey, Iraq, Azerbaijan, and Egypt has QGERRRKKR. In Indonesia it is QRESRRRKKR. In China it is the Fujian strain with LRERRRKR.
        In the past two years, there have been dramatic changes in the receptor binding domain, which are regionally present and not yet in humans. That list may grow in the upcoming season.
        In addition to the rapid evolution of the HA cleavage site, there is now rapid change in the receptor binding domain. Most of those changes are not in the above table. The most widely discussed is S227N (The above table should be labeled 214-228 (not 214-218) for the last domain listed.
        WHO is focused on positions 226 and 228 (with some interest in 190. New isolates in 2006 have a number of changes near the above three positions.
        S227N has been detected in 2 of the 4 human isolates from Turkey as well as one of the human isolates from Egypt at the beginning of this year.
        In birds however, the changes have been more dramatic this year.
        In the sequences released last week, 5 isolates from Shantou had three changes in this area (one was partial and had 2/3 - the third was not reported). These changes are K222R, V223I, and S227R (they also have V214M, which is not in the table).
        Isolates from Hunan have SIX changes (D187N, A189E, T192I, L184I, R220K, K222E).
        The isolate from Shanxi has FOUR changes (A188E, A189T, T192I, L194I).
        Since all of these isolates are from 2006, they are co-circulating, which offers the opportunity of more recombination to create more diversity, as is happening in the HA cleavage site.
        The affect of these various combinations has not been reported and many recent sequences have been withheld, especial HA sequences from northern China (as well as 6 of the 8 gene segments from southern China).
        It is these combinations of changes in a rapidly evolving H5N1 that is causing the concern.
        Last edited by GaudiaRay; November 12, 2006, 05:27 PM.

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        • #34
          Re: A list of relevant mutation position

          Oh! I did'nt see that a debate was goin on here.

          I want to thank Dr.Niman for adding the recent non-synonimus changes that apear in china this year. Clearly, the appearance of a wider variety of polymorphism at the protein level is of great concern.

          I see this as a new major turning point in the H5N1 viral evolution & I aggree that it goes just like the prevailing recombination theory would predict.

          My only comment to gsgs would be to download a reliable sequence alignement editor and align many different H5 sequences including some H3 & checkspot the right AA position based on a previously existing mutation list before compiling too many quantitative data.

          The standard numerotation is like the H3 position & some article count them with H5 position & there is some gap when we align H5 seq with H3's. False data will just fool everyones

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          • #35
            Re: A list of relevant mutation position

            >Re: A list of relevant mutation position
            >
            >
            >My simple question
            >to gsgs is "Do you agree with the facts stated below?" This is
            >a yes or no answer, with an explanation as to which points you
            >differ and wish to add commentary here.

            I'll read this later, going top to bottom

            >As a follow on question,
            > "Do you expect there to be more polymorphism changes in the near
            >term based on the fact that both the cleavage and receptor sites
            >now, this year, are showing previously unrecognized changes? If
            >yes, do you have a formula for the rate or the direction of those
            >changes? If no, why not?

            I see no reason to assume that evolution at the RBD or cleavage site
            is much different here than normal evolution of other areas in other
            flu-viruses. Well, except that it's in HA and in the antigenic sites
            maybe but that's probably not so important in birds.
            I could do some statistics and compare the rate of mutation
            (number of differences) in the RBD of H5 with other areas
            and other viruses.
            Maybe later ... Is it important/wanted ? ...

            >To help you gsgs in your response,
            > as I do wish for you to get an answer based on facts, not skewed
            >so heavily towards inquisitive thinking alone, here's what Niman
            >just posted elsewhere on the internet,
            >
            >> The Shanxi sequence,
            > with the multiple changes in or near the receptor binding domain
            >and the acquisition of mammalian polymorphisms in PB1 and MP was
            >isolated in 2006, as were the two related sequences from Hunan
            >and the five Shantou sequences.
            >
            >> The large number of changes
            >in an around the receptor binding domain of an H5N1 isolate is
            >without precedent, so a year ago there were ZERO such sequences
            >reported.

            well, when you look at my posted lists, you will find many changes in the
            RBD. How important/relevant they are is another question.
            That Nature paper seems to give some importance which is larger
            than any other changes.


            >> The story is in the sequence, and it is becoming
            >increasingly easy to read. <
            >
            >Yet, I will agree with you that
            >it's possible that one year ago, the virologists sequencing weren'
            >t looking that closesly at receptor binding domains as they are
            >now, and thus the changes being seen are no different than the
            >changes that occur each year. That's to be further explained,
            >maybe by you?

            I first noticed the importance of the RBD earlier this year.
            I remember the Scipps paper in March which examined them.
            The number of available human H5N1-sequences has greatly increased
            this year, so it's no surprise that the changes in the RBD also
            increase. Earlier we concentrated in the risistance-mutations,
            the virulence-mutations, the cleavage site.
            We should make a list of all important mutations to watch
            and _then_ see, which of them do happen for a better overview.

            We have lots of sequences from Indonesia meanwhile,
            most with the new cleavage site but no changes in the RBD.
            We have some changes in the RBD in China,Egypt, but most sequences
            still have them not.
            There is no indication yet that these changes did produce
            strains which can go pandemic.
            We could just have been lucky that they didn't.
            It should be tested how dangerous these changes are and how
            much they increase the contagiousness.

            Can't we infect larger populations of -say- ferrets with
            these viruses in a natural surrounding, maybe on an island
            or a closed,quarantined area and see, how it evolves ?

            I'm interested in expert panflu damage estimates
            my current links: http://bit.ly/hFI7H ILI-charts: http://bit.ly/CcRgT

            Comment

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