Reconstruction of the Evolutionary Dynamics of A(H3N2) Influenza Viruses Circulating in Italy from 2004 to 2012

PLoS One. 2015 Sep 2;10(9):e0137099. doi: 10.1371/journal.pone.0137099. eCollection 2015.

Abstract

Background: Influenza A viruses are characterised by their rapid evolution, and the appearance of point mutations in the viral hemagglutinin (HA) domain causes seasonal epidemics. The A(H3N2) virus has higher mutation rate than the A(H1N1) virus. The aim of this study was to reconstruct the evolutionary dynamics of the A(H3N2) viruses circulating in Italy between 2004 and 2012 in the light of the forces driving viral evolution.

Methods: Phylodinamic analyses were made using a Bayesian method, and codon-specific positive selection acting on the HA coding sequence was evaluated.

Results: Global and local phylogenetic analyses showed that the Italian strains collected between 2004 and 2012 grouped into five significant Italian clades that included viral sequences circulating in different epidemic seasons. The time of the most recent common ancestor (tMRCA) of the tree root was between May and December 2003. The tMRCA estimates of the major clades suggest that the origin of a new viral strain precedes the effective circulation of the strain in the Italian population by 6-31 months, thus supporting a central role of global migration in seeding the epidemics in Italy. The study of selection pressure showed that four codons were under positive selection, three of which were located in antigenic sites. Analysis of population dynamics showed the alternation of periods of exponential growth followed by a decrease in the effective number of infections corresponding to epidemic and inter-epidemic seasons.

Conclusions: Our analyses suggest that a complex interaction between the immune status of the population, migrations, and a few selective sweeps drive the influenza A(H3N2) virus evolution. Our findings suggest the possibility of the year-round survival of local strains even in temperate zones, a hypothesis that warrants further investigation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bayes Theorem
  • Evolution, Molecular*
  • Humans
  • Influenza A Virus, H3N2 Subtype / classification
  • Influenza A Virus, H3N2 Subtype / genetics*
  • Italy / epidemiology
  • Likelihood Functions
  • Phylogeny

Grants and funding

This work was supported by Fondazione Cariplo (grant No. 2011-0517, post-doc fellowships of LB and CV), the Marqués de Valdecilla University Hospital (grant No. WLA 03/1, pre-doctoral fellowship of MG), and partially supported by the national flagship project NANOMAX of the Italian Ministero dell' Università e della Ricerca.