Dynamically correlated mutations drive human Influenza A evolution

Human Influenza A virus undergoes recurrent changes in the hemagglutinin (HA) surface protein, primarily involved in the human antibody recognition. Relevant antigenic changes, enabling the virus to evade host immune response, have been recognized to occur in parallel to multiple mutations at antige...

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Bibliographic Details
Published in:Scientific reports 2013-09, Vol.3 (1), p.2705-2705, Article 2705
Main Authors: Tria, F, Pompei, S, Loreto, V
Format: Article
Language:English
Subjects:
Antigenic determinants
Antigens, Viral - genetics
Antigens, Viral - immunology
Epistasis
Epistasis, Genetic
Evolution, Molecular
Gene Frequency
Hemagglutinins
Host-Pathogen Interactions
Humans
Immune response
Influenza
Influenza A
Influenza A virus - classification
Influenza A virus - genetics
Influenza A virus - immunology
Influenza, Human - immunology
Influenza, Human - transmission
Influenza, Human - virology
Molecular evolution
Mutation
Phylogeny
Viruses
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Summary:Human Influenza A virus undergoes recurrent changes in the hemagglutinin (HA) surface protein, primarily involved in the human antibody recognition. Relevant antigenic changes, enabling the virus to evade host immune response, have been recognized to occur in parallel to multiple mutations at antigenic sites in HA. Yet, the role of correlated mutations (epistasis) in driving the molecular evolution of the virus still represents a challenging puzzle. Further, though circulation at a global geographic level is key for the survival of Influenza A, its role in shaping the viral phylodynamics remains largely unexplored. Here we show, through a sequence based epidemiological model, that epistatic effects between amino acids substitutions, coupled with a reservoir that mimics worldwide circulating viruses, are key determinants that drive human Influenza A evolution. Our approach explains all the up-to-date observations characterizing the evolution of H3N2 subtype, including phylogenetic properties, nucleotide fixation patterns, and composition of antigenic clusters.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep02705