tetano
Editor, Senior Moderator
Sci Rep. 2013 Sep 19;3:2705. doi: 10.1038/srep02705.
Dynamically correlated mutations drive human Influenza A evolution.
Tria F, Pompei S, Loreto V.
Source
Institute for Scientific Interchange (ISI), Via Alassio 11C, 10126 Torino, Italy.
Abstract
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.
PMID:
24048220
[PubMed - in process]
PMCID:
PMC3776956
Free PMC Article
http://www.ncbi.nlm.nih.gov/pubmed/24048220
Dynamically correlated mutations drive human Influenza A evolution.
Tria F, Pompei S, Loreto V.
Source
Institute for Scientific Interchange (ISI), Via Alassio 11C, 10126 Torino, Italy.
Abstract
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.
PMID:
24048220
[PubMed - in process]
PMCID:
PMC3776956
Free PMC Article
http://www.ncbi.nlm.nih.gov/pubmed/24048220