The monograph presents detailed analysis of influenza A/H1N1v-2009 gene and protein structure, compared to the previous pandemic influenza A strains. The monograph is aimed at virologists, molecular biologists, epidemiologists and physicians.
Genetic factors of virulence of pandemic influenza virus A/H1N1v-2009/10. Rapid development of sequence databases of influenza virus type A isolates leads to a large scale analysis for fine mapping of genetic determinants linked with virulence and pathogenicity. This approach is based on the comparative analysis of the gene and protein structure of currently obtained isolates with Spanish flu virus H1N1 (1918) and avian influenza highly pathogenic strains of H5N1. This clearly evidences that pathogenicity and virulence are polygenic signs which can be attributed to individual viral genes of genomic segments. Long-term studies showed that a combination of not less than 10 molecular signs of pathogenicity absent definitive genetic defects could determine viral pathogenicity. Pandemic virus H1N1v–2009 differs from its precursor H1N1, including recent isolates of 2008 year, or Spanish flu virus of 1918, and highly pathogenic strains of H5N1 viruses in connection with two key genetic defects: appearance of three stop–codons in PB1-F2 ORF, which leads to synthesis of short truncated 11 – amino acid residues polypeptide and extended C – terminal PDZ – binding s domain deletion in NS1 protein. On the basis of these two genetic defects, pandemic viruses are capable of being classified as moderate in virulence and pathogenicity. Accumulation of mutations in specific domains of viral protein during active circulation may contribute to a sudden increase of pathogenicity and be linked with severe, complicated and fatal form of influenza illness. They include mutations in HA protein which are involved in the creation of the Scorpion toxin-like domains or in the receptor-binding site – D222G.
Book review by Nikolai Kaverin is published in Voprosy Virusologii (Problems of Virology), 2012, Vol.6, p. 46-47. (Russian)
