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

Ebranati E, Pariani E, Piralla A, Gozalo-Margüello M, Veo C, Bubba L, Amendola A, Ciccozzi M, Galli M, Zanetti AR, Baldanti F, Zehender G - PLoS ONE (2015)

Bottom Line: 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.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.Our findings suggest the possibility of the year-round survival of local strains even in temperate zones, a hypothesis that warrants further investigation.

View Article: PubMed Central - PubMed

Affiliation: Dipartimento di Scienze Biomediche e Cliniche "Luigi Sacco", Sezione di Malattie Infettive, Università degli Studi di Milano, Milan, Italy.

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.

No MeSH data available.


Related in: MedlinePlus

Amino acid changes in the antigenic sites domain in the A/Aichi/2/68(H3N2) influenza strain in eight consecutive seasons.The dots represent amino acids similar to those in the A/Aichi/2/68(H3N2) strain. The number of sequences analysed in each season is shown in brackets. The number of strains observed for each single amino acid substitution is shown in subscript.
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pone.0137099.g002: Amino acid changes in the antigenic sites domain in the A/Aichi/2/68(H3N2) influenza strain in eight consecutive seasons.The dots represent amino acids similar to those in the A/Aichi/2/68(H3N2) strain. The number of sequences analysed in each season is shown in brackets. The number of strains observed for each single amino acid substitution is shown in subscript.

Mentions: The HA1 domain of HA contains all the H3 antigenic sites A-E. Fig 2 summarises the amino acid changes observed in the antigenic sites of the A/Aichi/2/1968(H3N2) virus. A total of 41/106 amino acid positions (38.7%) had at least one change, all of which were observed in the influenza strains circulating in the 2003–2004 season (Fig 1). However, a few key substitutions were observed during subsequent seasons: in 2005–2006, substitution S193F was accompanied by substitution D225N (Figs 1 and 2) in 2008–2009, a K158N substitution in antigenic site B1 was sporadically observed but became fixed in the following seasons; substitution T212A observed in HA sequences from season 2010–2011 was retained in sequences from the 2011–2012 season; and, in 2011–2012, a series of amino acid substitutions (D53N, N144D and N145S) were similar to those observed in the “older” A/Aichi/2/68 strain (in particular, substitution N144D generated the loss of an NGS site in position 144.


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

Ebranati E, Pariani E, Piralla A, Gozalo-Margüello M, Veo C, Bubba L, Amendola A, Ciccozzi M, Galli M, Zanetti AR, Baldanti F, Zehender G - PLoS ONE (2015)

Amino acid changes in the antigenic sites domain in the A/Aichi/2/68(H3N2) influenza strain in eight consecutive seasons.The dots represent amino acids similar to those in the A/Aichi/2/68(H3N2) strain. The number of sequences analysed in each season is shown in brackets. The number of strains observed for each single amino acid substitution is shown in subscript.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4558001&req=5

pone.0137099.g002: Amino acid changes in the antigenic sites domain in the A/Aichi/2/68(H3N2) influenza strain in eight consecutive seasons.The dots represent amino acids similar to those in the A/Aichi/2/68(H3N2) strain. The number of sequences analysed in each season is shown in brackets. The number of strains observed for each single amino acid substitution is shown in subscript.
Mentions: The HA1 domain of HA contains all the H3 antigenic sites A-E. Fig 2 summarises the amino acid changes observed in the antigenic sites of the A/Aichi/2/1968(H3N2) virus. A total of 41/106 amino acid positions (38.7%) had at least one change, all of which were observed in the influenza strains circulating in the 2003–2004 season (Fig 1). However, a few key substitutions were observed during subsequent seasons: in 2005–2006, substitution S193F was accompanied by substitution D225N (Figs 1 and 2) in 2008–2009, a K158N substitution in antigenic site B1 was sporadically observed but became fixed in the following seasons; substitution T212A observed in HA sequences from season 2010–2011 was retained in sequences from the 2011–2012 season; and, in 2011–2012, a series of amino acid substitutions (D53N, N144D and N145S) were similar to those observed in the “older” A/Aichi/2/68 strain (in particular, substitution N144D generated the loss of an NGS site in position 144.

Bottom Line: 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.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.Our findings suggest the possibility of the year-round survival of local strains even in temperate zones, a hypothesis that warrants further investigation.

View Article: PubMed Central - PubMed

Affiliation: Dipartimento di Scienze Biomediche e Cliniche "Luigi Sacco", Sezione di Malattie Infettive, Università degli Studi di Milano, Milan, Italy.

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.

No MeSH data available.


Related in: MedlinePlus