Molecular Epidemiology of Influenza A/H3N2 Viruses Circulating in Mexico from 2003 to 2012

<div><p>In this work, nineteen influenza A/H3N2 viruses isolated in Mexico between 2003 and 2012 were studied. Our findings show that different human A/H3N2 viral lineages co-circulate within a same season and can also persist locally in between different influenza seasons, increasing the chance for genetic reassortment events. A novel minor cluster was also identified, named here as Korea, that circulated worldwide during 2003. Frequently, phylogenetic characterization did not correlate with the determined antigenic identity, supporting the need for the use of molecular evolutionary tools additionally to antigenic data for the surveillance and characterization of viral diversity during each flu season. This work represents the first long-term molecular epidemiology study of influenza A/H3N2 viruses in Mexico based on the complete genomic sequences and contributes to the monitoring of evolutionary trends of A/H3N2 influenza viruses within North and Central America.</p></div

Properties of A/H3N2 Mexican Isolates and reference strains used in analysis.

1<p>As determined by standard haemagglutination inhibition assay.</p>2<p>As determined in this work.</p>3<p>Not determined.</p>4<p>A/Korea/770/2002 was determined as antigenically equivalent to the A/Fujian/411/02 vaccine strain <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102453#pone.0102453-Daum1" target="_blank">[48]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102453#pone.0102453-Kang1" target="_blank">[49]</a>.</p>5<p>Accession numbers of reference strain segments used in analysis.</p

Phylogenetic analysis based on the coding sequence of the HA gene of 19 samples isolated in Mexico from 2003 to 2012.

<p>The tree was built using the ML criteria with a background of 758 selected human A/H3N2 influenza viruses from North America. Support values were determined by aLRT and only values ≥0.70 are shown for significant nodes. The tree is mid-point rooted for purposes of clarity, and all horizontal branches are drawn to scale. Different coloring in branches indicate seasonality, as established by virus collection dates (from January to June, and from July to December, respectively). Viruses from before the 2002–2003 season are shown black. The position of the Mexican isolates in the tree is indicated by coding letters, as depicted in the left portion of figure.</p

Mutations in the HA and M2 proteins.

1<p>Determined by HA2 numbering (+16 from aminoacid one in coding sequence, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102453#pone.0102453-Jin1" target="_blank">[39]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0102453#pone.0102453-Wiley1" target="_blank">[40]</a>.</p>2<p>Amantadine sensitivity given by mutation in position 31 of M2 protein. S = sensitivity, N = resistance.</p>3<p>Antigenic sites B and E are conformational epitopes.</p>4<p>Changes of interest are shown in bold and italics.</p