WHO Collaborating Center for Influenza, Centers for Disease Control and Prevention, USA.
Since its identification in April 2009 an A(H1N1) virus containing a unique combination of gene segments from both North American and Eurasian swine lineages has continued to circulate in humans. The lack of similarity between the 2009 A(H1N1) virus and its nearest relatives indicates that its gene segments have been circulating undetected for an extended period. Its low genetic diversity suggests the introduction into humans was a single event or multiple events of similar viruses. Molecular markers predictive of adaptation to humans are not currently present in 2009 A(H1N1) viruses, suggesting previously unrecognized molecular determinants could be responsible for the transmission among humans. Antigenically the viruses are homogeneous and similar to North American swine A(H1N1) viruses but distinct from seasonal human A(H1N1).
Showing posts with label swine flue. Show all posts
Showing posts with label swine flue. Show all posts
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New 3-D structural model of critical H1N1 protein developed
Singapore scientists conduct and complete research in just two weeks
In just two weeks from the time the first patient virus samples were made available, Singapore scientists report an evolutionary analysis of a critical protein produced by the 2009 H1N1 influenza A virus strain.
In the Biology Direct journal's May 20th issue, Sebastian Maurer-Stroh, Ph.D., and his team of scientists at the Bioinformatics Institute (BII), one of the research institutes at Singapore's Biopolis, also demonstrated the use of a computational 3-dimensional (3D) structural model of the protein, neuraminidase.
"Because we were working as a team, driven by the common goal to understand potential risks from this new virus, our group at BII was able to successfully complete this difficult analysis within such a short time," said Dr. Maurer-Stroh, BII principal investigator and first author of the paper.
BII's interactive 3D model is available at the following link: http://mendel.bii.a-star.edu.sg/SEQUENCES/H1N1/
With the 3D model, Dr. Maurer-Stroh and his team were able to map the regions of the protein that have mutated and determine whether drugs and vaccines that target specific areas of the protein were effective. Among their findings:
a. neuraminidase structure of the 2009 H1N1 influenza A virus has undergone extensive surface mutations compared to closely related strains such as the H5N1 avian flu virus or other H1N1 strains including the 1918 Spanish flu;
b. neuraminidase of the 2009 H1N1 influenza A virus strain is more similar to the H5N1 avian flu than to the historic 1918 H1N1 strain (Spanish flu);
c. current mutations of the virus have rendered previous flu vaccinations directed against neuraminidase less effective; and
d. commercial drugs, namely Tamiflu® and Relenza®, are still effective in treating the current H1N1 virus.
With the Biology Direct journal paper, the Singapore scientists have become the first to demonstrate how bioinformatics and computational biology can contribute towards managing the H1N1 influenza A virus.
"BII's H1N1 virus sequence study marks a significant milestone in the use of computational biology methods in understanding how the mutations of the fast evolving influenza virus affect immunogenic properties or drug response," said BII Director Frank Eisenhaber, Ph.D. "This information helps to develop a strategy for fighting the H1N1 virus and for organising an effective treatment for patients."
Other technologies to tackle the 2009 H1N1 Influenza A virus have been developed by scientists at Biopolis research institutes sponsored by Singapore's A*STAR (Agency for Science, Technology and Research). They include:
a chip that is able to quickly sequence or decode the genes in the flu virus and distinguish between the H1N1, seasonal, and mutated flu strains, at the Genome Institute of Singapore (GIS).
a microkit for the detection and identification of the flu virus strain within 2 hours, at the Institute of Bioengineering and Nanotechnology (IBN).
a molecular diagnostic assay to distinguish between the H1N1 and seasonal flu strains, at the Institute of Molecular and Cell Biology (IMCB).
###
The Singapore scientists' paper, "Mapping the sequence mutations of the 2009 H1N1 influenza A virus neuraminidase relative to drug and antibody binding sites," was published in Biology Direct journal on 20 May 2009. Authors: Sebastian Maurer-Stroh1, Jianmin Ma1, Raphael Tze Chuen Lee1, Fernanda L Sirota1 and Frank Eisenhaber1,2
1Biomolecular Function Discovery Division, Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), Singapore 2Department of Biological Sciences, National University of Singapore, Singapore
Influenza A virus strains are categorized according to two proteins found on the surface of the virus: haemagglutinin (H) and neuraminidase (N). All influenza A viruses contain haemagglutinin and neuraminidase. The structures of these proteins differ from strain to strain eg, swine flu belongs to the H1N1 type, avian flu to H5N1 and the currently dominant seasonal flu belongs to the H3N2 type.
In just two weeks from the time the first patient virus samples were made available, Singapore scientists report an evolutionary analysis of a critical protein produced by the 2009 H1N1 influenza A virus strain.
In the Biology Direct journal's May 20th issue, Sebastian Maurer-Stroh, Ph.D., and his team of scientists at the Bioinformatics Institute (BII), one of the research institutes at Singapore's Biopolis, also demonstrated the use of a computational 3-dimensional (3D) structural model of the protein, neuraminidase.
"Because we were working as a team, driven by the common goal to understand potential risks from this new virus, our group at BII was able to successfully complete this difficult analysis within such a short time," said Dr. Maurer-Stroh, BII principal investigator and first author of the paper.
BII's interactive 3D model is available at the following link: http://mendel.bii.a-star.edu.sg/SEQUENCES/H1N1/
With the 3D model, Dr. Maurer-Stroh and his team were able to map the regions of the protein that have mutated and determine whether drugs and vaccines that target specific areas of the protein were effective. Among their findings:
a. neuraminidase structure of the 2009 H1N1 influenza A virus has undergone extensive surface mutations compared to closely related strains such as the H5N1 avian flu virus or other H1N1 strains including the 1918 Spanish flu;
b. neuraminidase of the 2009 H1N1 influenza A virus strain is more similar to the H5N1 avian flu than to the historic 1918 H1N1 strain (Spanish flu);
c. current mutations of the virus have rendered previous flu vaccinations directed against neuraminidase less effective; and
d. commercial drugs, namely Tamiflu® and Relenza®, are still effective in treating the current H1N1 virus.
With the Biology Direct journal paper, the Singapore scientists have become the first to demonstrate how bioinformatics and computational biology can contribute towards managing the H1N1 influenza A virus.
"BII's H1N1 virus sequence study marks a significant milestone in the use of computational biology methods in understanding how the mutations of the fast evolving influenza virus affect immunogenic properties or drug response," said BII Director Frank Eisenhaber, Ph.D. "This information helps to develop a strategy for fighting the H1N1 virus and for organising an effective treatment for patients."
Other technologies to tackle the 2009 H1N1 Influenza A virus have been developed by scientists at Biopolis research institutes sponsored by Singapore's A*STAR (Agency for Science, Technology and Research). They include:
a chip that is able to quickly sequence or decode the genes in the flu virus and distinguish between the H1N1, seasonal, and mutated flu strains, at the Genome Institute of Singapore (GIS).
a microkit for the detection and identification of the flu virus strain within 2 hours, at the Institute of Bioengineering and Nanotechnology (IBN).
a molecular diagnostic assay to distinguish between the H1N1 and seasonal flu strains, at the Institute of Molecular and Cell Biology (IMCB).
###
The Singapore scientists' paper, "Mapping the sequence mutations of the 2009 H1N1 influenza A virus neuraminidase relative to drug and antibody binding sites," was published in Biology Direct journal on 20 May 2009. Authors: Sebastian Maurer-Stroh1, Jianmin Ma1, Raphael Tze Chuen Lee1, Fernanda L Sirota1 and Frank Eisenhaber1,2
1Biomolecular Function Discovery Division, Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), Singapore 2Department of Biological Sciences, National University of Singapore, Singapore
Influenza A virus strains are categorized according to two proteins found on the surface of the virus: haemagglutinin (H) and neuraminidase (N). All influenza A viruses contain haemagglutinin and neuraminidase. The structures of these proteins differ from strain to strain eg, swine flu belongs to the H1N1 type, avian flu to H5N1 and the currently dominant seasonal flu belongs to the H3N2 type.
Mapping the sequence mutations of the 2009 H1N1 influenza A virus neuraminidase relative to drug and antibody binding sites
Maurer-Stroh S, Ma J, Lee RT, Sirota FL, Eisenhaber F.
ABSTRACT: In this work, we study the consequences of sequence variations of the "2009 H1N1" (swine or Mexican flu) influenza A virus strain neuraminidase for drug treatment and vaccination. We find that it is phylogenetically more closely related to European H1N1 swine flu and H5N1 avian flu rather than to the H1N1 counterparts in the Americas. Homology-based 3D structure modeling reveals that the novel mutations are preferentially located at the protein surface and do not interfere with the active site.
The latter is the binding cavity for 3 currently used neuraminidase inhibitors: oseltamivir (Tamiflu(R)), zanamivir (Relenza(R)) and peramivir; thus, the drugs should remain effective for treatment. However, the antigenic regions of the neuramidase relevant for vaccine development, serological typing and passive antibody treatment can differ from those of previous strains and already vary among patients.
Reviewers: This article was reviewed by Sandor Pongor and Aravind Lakshminarayanan Iyer
ABSTRACT: In this work, we study the consequences of sequence variations of the "2009 H1N1" (swine or Mexican flu) influenza A virus strain neuraminidase for drug treatment and vaccination. We find that it is phylogenetically more closely related to European H1N1 swine flu and H5N1 avian flu rather than to the H1N1 counterparts in the Americas. Homology-based 3D structure modeling reveals that the novel mutations are preferentially located at the protein surface and do not interfere with the active site.
The latter is the binding cavity for 3 currently used neuraminidase inhibitors: oseltamivir (Tamiflu(R)), zanamivir (Relenza(R)) and peramivir; thus, the drugs should remain effective for treatment. However, the antigenic regions of the neuramidase relevant for vaccine development, serological typing and passive antibody treatment can differ from those of previous strains and already vary among patients.
Reviewers: This article was reviewed by Sandor Pongor and Aravind Lakshminarayanan Iyer
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