Reconstruction of the Evolutionary Dynamics of A(H3N2) Influenza Viruses Circulating in Italy from 2004 to 2012.
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.
Dipartimento di Scienze Biomediche e Cliniche "Luigi Sacco", Sezione di Malattie Infettive, Università degli Studi di Milano, Milan, Italy.
Erika
E
Ebranati
Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy.
Elena
E
Pariani
SS Virologia Molecolare, SC Virologia e Microbiologia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Antonio
A
Piralla
SS Virologia Molecolare, SC Virologia e Microbiologia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Marqués de Valdecilla University Hospital, Santander, Spain.
Monica
M
Gozalo-Margüello
Dipartimento di Scienze Biomediche e Cliniche "Luigi Sacco", Sezione di Malattie Infettive, Università degli Studi di Milano, Milan, Italy.
Carla
C
Veo
Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy.
Laura
L
Bubba
Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy.
Antonella
A
Amendola
Istituto Superiore di Sanità, Dipartimento Malattie Infettive, Parassitarie ed Immunomediate, Rome, Italy.
Massimo
M
Ciccozzi
Dipartimento di Scienze Biomediche e Cliniche "Luigi Sacco", Sezione di Malattie Infettive, Università degli Studi di Milano, Milan, Italy.
Massimo
M
Galli
Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Milan, Italy.
Alessandro Remo
AR
Zanetti
SS Virologia Molecolare, SC Virologia e Microbiologia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Fausto
F
Baldanti
Dipartimento di Scienze Biomediche e Cliniche "Luigi Sacco", Sezione di Malattie Infettive, Università degli Studi di Milano, Milan, Italy.
Gianguglielmo
G
Zehender
D001499:Bayes Theorem; D019143:Evolution, Molecular; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000145:classification / Q000235:genetics*; D007558:Italy / Q000453:epidemiology; D016013:Likelihood Functions; D010802:Phylogeny