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Molecular Characteristics And Functions Of The H1n1 Influenza Virus Strain Analysis And Forecasting

Posted on:2011-03-31Degree:MasterType:Thesis
Country:ChinaCandidate:J MengFull Text:PDF
GTID:2204360305951454Subject:Pathogen Biology
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In April 2009, a new type of flu originated in Mexico raises a panic. Within just a few weeks, the new flu virus rapidly spread over the world. On the June 11th,2009, the WHO raised the global influenza pandemic warning level to the highest level-the sixth grade, China is one of the hardest hit areas, and it makes no exception of and Shandong Province. This flu affects people's normal life.The flu virus outbroken this time is a new type of influenza virus; we use the structural bioinformatics approach to analyze the molecular characteristics of strains of the virus in Shandong Province systematically, and to predict its function. By molecular phylogenetic analysis, strains in Shandong Province are the hemagglutinin (HA) 1-type, neuraminidase (NA) 1-type strain. The genome of the strains sourced from human, pig, bird flu genetic material is a four-rearrangement of influenza A virus. The HA, NP and NS genes source from classical swine H1N1 subtype of influenza strains, NA and MP genes source from avian H1N1 subtype of swine influenza virus strain. PA and PB2 genes source from different subtypes of avian influenza virus, and PB1 gene source from seasonal human influenza virus subtype H3N2. Although the 8 gene fragments of this new Influenza A H1N1 influenza virus formed different evolutionary trees, there are still some similarities:four new strains of influenza pandemic A H1N1 A/Mexico/4486/2009; A/California/04/2009; A/ Beijing/3/2009 (H1N1) and A/Shandong/1/2009 together formed an independent evolutionary branch, and were supported by high value of Bootstrap It shows that the new influenza virus A H1N1 in 2009 have a common evolutionary ancestor, H1N1 influenza virus have no significant variation during the spreading process.The analysis of its hemagglutinin structure, surface potential and molecular docking indicates that the influenza A H1N1 influenza virus receptor binding site was completely identical to the typical amino acid of human influenza virus, which means that the specificity of receptor-binding protein in those new influenza A H1N1 influenza virus compliance with the requirements of infecting human, and has the molecular basis of spreading among human. To a certain extent, it explains the phenomenon why the H1N1 influenza virus only spread from human to human, but seldom spread between human and swine. The analysis of the glycosylation and lipid sites in the strains of HA protein indicates that the glycosylation sites in HA strains protein are only 27,28,40,104, 286,304, and 498, less than other seasonal influenza viruses, and have no changes in lipid sites and disulfide bond sites. Shandong strain has fewer glycosylation sites, suggesting that the influenza virus have a strong virulence. Through the Sequence-based and structure-based epitope analysis, we found the epitopes of the HA strains of Shandong Province are mainly located in the head of the protein, compaing with the strain in Australia, the epitome Cal area 222 mutates (Lys to Arg), and has no obvious change compared with the strain of the Americas 2009, so the relevant vaccine from those strains which are provided by WHO should be effective. The analysis and prediction of NA protein structure indicate that compared to other seasonal influenza NA, the NA mutation of amino acid sites are mainly located in the molecular surface outside the active site, but did not occur in the active sites of NA enzyme. So drugs targeted at the NA protein should be effective.Based on the analysis of Shandong Province strain gene sequences, protein sequences, protein structure, surface properties of molecules, and the rapid analysis of molecular docking of epitopes, drugs target site, the initial establishment of a rapid setting, analysis, forecast the structure of biological information Methodology have been accomplished, it should have a reference to prevent and control the influenza A virus, especially for the current basis and situation of disease control in Shandong Province, the method in this article attributes to a transformation of appropriate control techniques from relying on experiences to rational consideration, especially with the development of a new generation of low-cost, high-throughput sequencing technology, the structural bioinformatics approach will become the mainstream technology, directing the control and prevention of pandemic diseases in new situations.
Keywords/Search Tags:Influenza A virus, H1N1, HA, NA, Bioinformatics analysis
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