Phylogeography of the spring and fall waves of the H1N1/09 pandemic influenza virus in the United States

Abstract

Spatial variation in the epidemiological patterns of successive waves of pandemic influenza virus in humans has been documented throughout the 20th century but never understood at a molecular level. However, the unprecedented intensity of sampling and whole-genome sequencing of the H1N1/09 pandemic virus now makes such an approach possible. To determine whether the spring and fall waves of the H1N1/09 influenza pandemic were associated with different epidemiological patterns, we undertook a large-scale phylogeographic analysis of viruses sampled from three localities in the United States. Analysis of genomic and epidemiological data reveals distinct spatial heterogeneities associated with the first pandemic wave, March to July 2009, in Houston, TX, Milwaukee, WI, and New York State. In Houston, no specific H1N1/09 viral lineage dominated during the spring of 2009, a period when little epidemiological activity was observed in Texas. In contrast, major pandemic outbreaks occurred at this time in Milwaukee and New York State, each dominated by a different viral lineage and resulting from strong founder effects. During the second pandemic wave, beginning in August 2009, all three U.S. localities were dominated by a single viral lineage, that which had been dominant in New York during wave 1. Hence, during this second phase of the pandemic, extensive viral migration and mixing diffused the spatially defined population structure that had characterized wave 1, amplifying the one viral lineage that had dominated early on in one of the world's largest international travel centers.

FIG. 1.

Proportion of all emergency department visits that are coded as influenza in Houston, Milwaukee, and New York State, 2009 to 2010. Data collected by SDI, Plymouth Meeting, PA. Peaks in influenza virus activity associated with the 2008-2009 seasonal H1N1 epidemic (shaded green), the spring wave of pandemic H1N1/09 viruses (shaded red), and the fall wave of pandemic H1N1/09 viruses (shaded blue) are depicted.

FIG. 2.

Evolutionary relationships of the concatenated whole-genome sequences from 674 sequences of pandemic H1N1/09 viruses collected in North America during the first pandemic wave, from 1 April 2009 to 29 July 2009. The maximum likelihood (ML) tree is midpoint rooted for clarity, with all branch lengths drawn to scale. Numbers on branches indicate approximate likelihood ratio test values and provide an indication of statistical support for individual nodes. Sequences shaded in orange were collected in New York State; sequences shaded in green were collected in Milwaukee; sequences shaded in blue were collected in Houston; sequences shaded in black were collected in other North American localities.

FIG. 3.

Evolutionary relationships of the concatenated whole-genome sequences from 638 sequences of pandemic H1N1/09 viruses collected in North America during the second pandemic wave, from 5 August 2009 to 3 March 2010. All rooting, labels, and color coding are identical to those used in Fig. 2.