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BMC. Identification of hemagglutinin structural domain and polymorphisms which may modulate swine H1N1 interactions with human receptor

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  • BMC. Identification of hemagglutinin structural domain and polymorphisms which may modulate swine H1N1 interactions with human receptor

    Identification of hemagglutinin structural domain and polymorphisms which may modulate swine H1N1 interactions with human receptor (BMC, abstract, edited)
    Identification of hemagglutinin structural domain and polymorphisms which may modulate swine H1N1 interactions with human receptor

    Veljko Veljkovic, Henry L Niman, Sanja Glisic, Nevena Veljkovic, Vladimir Perovic and Claude P Muller

    BMC Structural Biology 2009, 9:62doi:10.1186/1472-6807-9-62
    Published: 28 September 2009


    Abstract (provisional)

    Background
    The novel A/H1N1 influenza virus, which recently emerged in North America is most closely related to North American H1N1/N2 swine viruses. Until the beginning of 2009, North American swine H1N1/N2 viruses have only sporadically infected humans as dead-end hosts. In 2009 the A/H1N1 virus acquired the capacity to spread efficiently by human to human transmission. The novel A/H1N1 influenza virus has struck thousands of people in more than 70 countries and killed more than 140, representing a public health emergency of international concern. Here we have studied properties of hemagglutinin of A/H1N1 which may modulate virus/receptor interaction.

    Results
    Analyses by ISM bioinformatics platform of the HA1 protein of North American swine H1N1/N2 viruses and the new A/H1N1 showed that both groups of viruses differed in conserved characteristics that reflect a distinct propensity of these viruses to undergo a specific interaction with swine or human host proteins or receptors. Swine H1N1/N2 viruses that sporadically infected humans featured both the swine and the human interaction pattern. Substitutions F71S, T128S, E302K, M314L in HA1 of swine H1N1 viruses from North America are identified as critical for the human interaction pattern of A/H1N1 and residues D94, D196 and D274 are predicted to be "hot-spots" for polymorphisms which could increase infectivity of A/H1N1 virus. At least one of these residues has already emerged in the A/H1N1 isolates from Spain, Italy and USA. The domain 286-326 was identified to be involved in virus/receptor interaction.

    Conclusions
    Our results
    (i) contribute to better understanding of the origin of the novel A/H1N1 influenza virus,
    (ii) provide a tool for monitoring its molecular evolution
    (iii) predicts hotspots associated with enhanced infectivity in humans and
    (iv) identify therapeutic and diagnostic targets for prevention and treatment of A/H1N1 infection.
    -
    <cite cite="http://www.biomedcentral.com/1472-6807/9/62/abstract">Abstract | Identification of hemagglutinin structural domain and polymorphisms which may modulate swine H1N1 interactions with human receptor</cite>
    Attached Files

  • #2
    Identification of hemagglutinin structural domain and polymorphisms which may modulate swine H1N1 interactions with human receptor

    EXTRACT. Full paper at http://www.biomedcentral.com/1472-6807/9/62

    Identification of hemagglutinin structural domain and polymorphisms which may modulate swine H1N1 interactions with human receptor

    Veljko Veljkovic1, Henry L Niman, Sanja Glisic1, Nevena Veljkovic1, Vladimir Perovic1 and Claude P Muller

    Received: 18 June 2009
    Accepted: 28 September 2009
    Published: 28 September 2009

    Background

    The novel A/H1N1 influenza virus, which recently emerged in North America is most closely related to North American H1N1/N2 swine viruses. Until the beginning of 2009, North American swine H1N1/N2 viruses have only sporadically infected humans as dead-end hosts. In 2009 the A/H1N1 virus acquired the capacity to spread efficiently by human to human transmission. The novel A/H1N1 influenza virus has struck thousands of people in more than 70 countries and killed more than 140, representing a public health emergency of international concern. Here we have studied properties of hemagglutinin of A/H1N1 which may modulate virus/receptor interaction.
    Results

    Analyses by ISM bioinformatics platform of the HA1 protein of North American swine H1N1/N2 viruses and the new A/H1N1 showed that both groups of viruses differed in conserved characteristics that reflect a distinct propensity of these viruses to undergo a specific interaction with swine or human host proteins or receptors. Swine H1N1/N2 viruses that sporadically infected humans featured both the swine and the human interaction pattern. Substitutions F71S, T128S, E302K, M314L in HA1 of swine H1N1 viruses from North America are identified as critical for the human interaction pattern of A/H1N1 and residues D94, D196 and D274 are predicted to be "hot-spots" for polymorphisms which could increase infectivity of A/H1N1 virus. At least one of these residues has already emerged in the A/H1N1 isolates from Spain, Italy and USA. The domain 286-326 was identified to be involved in virus/receptor interaction.

    Comment


    • #3
      Re: Identification of hemagglutinin structural domain and polymorphisms which may modulate swine H1N1 interactions with human receptor

      Originally posted by Hogweed View Post
      .........Veljko Veljkovic1, Henry L Niman, Sanja Glisic1, Nevena Veljkovic1, Vladimir Perovic1 and Claude P Muller...........
      1Center for Multidisciplinary Research, Institute of Nuclear Sciences VINCA, P.O. Box 522, 11001 Belgrade, Serbia

      2Recombinomics, Inc., 648 Field Club Road, Pittsburgh, PA 15238, USA

      3Institute of Immunology Laboratoire National de Sant?/CRP-Sant?, Luxembourg, 20A rue Auguste Lumi?re, L-1950 Luxembourg, Grand-Duchy of Luxembourg

      ---------------------------------------------------------------------------------------
      (snipped)

      Conclusion

      Analyses by the ISM bioinformatics platform of the HA1 protein of North American swine H1N1 and H1N2 viruses and the new A/H1N1 that emerged recently in Mexico and the USA showed that both groups of viruses differed in characteristic parameters that reflect a distinct propensity of these viruses to undergo a specific interaction with swine or human host proteins or receptors. Using the same approach, amino acid substitutions F71S, T128S, E302K, M314L in the A/H1N1 HA1 essential for the human interaction pattern of these viruses were identified and residues 94D, 196D and 274D of A/H1N1 HA1 were predicted as "hot-spots" for mutations that may significantly increase the propensity of this virus to interact preferentially with human host proteins. At least one of these mutations (D274E) was already found in the A/H1N1 isolates from Spain, Italy and US, suggesting the virus further adapts to the human host. In addition, it has been suggested that the highly conserved domain 286 - 326 of HA1 plays an important role in A/H1N1-receptor interaction and represents a candidate target for diagnostics, vaccines and therapies.

      Background The novel A/H1N1 influenza virus, which recently emerged in North America is most closely related to North American H1N1/N2 swine viruses. Until the beginning of 2009, North American swine H1N1/N2 viruses have only sporadically infected humans as dead-end hosts. In 2009 the A/H1N1 virus acquired the capacity to spread efficiently by human to human transmission. The novel A/H1N1 influenza virus has struck thousands of people in more than 70 countries and killed more than 140, representing a public health emergency of international concern. Here we have studied properties of hemagglutinin of A/H1N1 which may modulate virus/receptor interaction. Results Analyses by ISM bioinformatics platform of the HA1 protein of North American swine H1N1/N2 viruses and the new A/H1N1 showed that both groups of viruses differed in conserved characteristics that reflect a distinct propensity of these viruses to undergo a specific interaction with swine or human host proteins or receptors. Swine H1N1/N2 viruses that sporadically infected humans featured both the swine and the human interaction pattern. Substitutions F71S, T128S, E302K, M314L in HA1 of swine H1N1 viruses from North America are identified as critical for the human interaction pattern of A/H1N1 and residues D94, D196 and D274 are predicted to be "hot-spots" for polymorphisms which could increase infectivity of A/H1N1 virus. At least one of these residues has already emerged in the A/H1N1 isolates from Spain, Italy and USA. The domain 286-326 was identified to be involved in virus/receptor interaction. Conclusion Our results (i) contribute to better understanding of the origin of the novel A/H1N1 influenza virus, (ii) provide a tool for monitoring its molecular evolution (iii) predicts hotspots associated with enhanced infectivity in humans and (iv) identify therapeutic and diagnostic targets for prevention and treatment of A/H1N1 infection.
      "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

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