Contemporary epidemiology of North American lineage triple reassortant influenza A viruses in pigs

Abstract

The 2009 pandemic H1N1 infection in humans has been one of the greatest concerns for public health in recent years. However, influenza in pigs is a zoonotic viral disease well-known to virologists for almost one century with the classical H1N1 subtype the only responsible agent for swine influenza in the United States for many decades. Swine influenza was first recognized clinically in pigs in the Midwestern U.S. in 1918 and since that time it has remained important to the swine industry throughout the world. Since 1988, however, the epidemiology of swine influenza changed dramatically. A number of emerging subtypes and genotypes have become established in the U.S. swine population. The ability of multiple influenza virus lineages to infect pigs is associated with the emergence of reassortant viruses with new genomic arrangements, and the introduction of the 2009 pandemic H1N1 from humans to swine represents a well-known example. The recent epidemiological data regarding the current state of influenza A virus subtypes circulating in the Canadian and American swine population is discussed in this review.

Fig. 1

Epidemiology and genetic composition of influenza viruses from U.S. and Canadian pigs. Swine virus lineage is color coded pink, avian lineage is coded green, human lineage is coded blue or purple. The chronology of transmission events leading to reassortant viruses with genes from swine, human and avian influenza virus lineages is visualized by the vertical arrow. The “Spanish flu” virus was transmitted from avian/human origin to pigs and evolved into the cH1N1, as indicated by the transition in color of pigs from blue to light blue to red to pink. The human and avian images to the left of the vertical timeline represent the species origin of viral gene segments donated to give rise to the swine influenza virus reassortants listed on the right side of the vertical timeline. Time line is not drawn to scale. Each viral subtype is represented with its eight gene segment arrangement. The triple reassortant H3N2 reassorted with the cH1N1 to produce rH1N1 and H1N2 subtypes with the triple reassortant internal gene (TRIG) cassette. Further reassortment events with two independent human H1 subtype viruses led to the δ1 H1N2 and δ2 H1N1. The source of the reassortment event producing the combination of gene segments in the 2009 pandemic H1N1 prior to its emergence in human and subsequent transmission from humans to pigs in 2009 is currently unknown. Light green indicates the Eurasian avian/swine lineage. The gray highlighted area illustrates the currently circulating influenza A subtypes in Canadian and American pigs

Fig. 2

Neighbor-joining trees inferred from multiple nucleotide sequence alignment of segment 4 (HA, a) and segment 6 (NA, 2b). a shows four H1 clusters of viruses, H1α, H1β, H1γ and H1δ (human-like H1) as indicated by the bars on the right of the tree. In both trees, the HA cluster specificity is indicated. The genomic constellation of each clade is indicated by the images on the right side of the tree. Classical swine lineage is color coded pink, avian lineage is coded green, human lineage is coded blue or purple. Light green indicates the Eurasian avian/swine lineage. Classical swine lineage-HA gene (a) was acquired by the TRIG cassette and evolved overtime to form α-, β- and γ- clusters. The introduction of human seasonal HA from H1N2 and H1N1 gave rise to δ cluster viruses differentiated phylogenetically by two distinct sub-clusters, δ1 and δ2 (a). Similar to the δ-cluster viruses in the HA phylogenetic analysis, β-viruses have split into two sub-clusters (b). Phylogenetic analyzes were conducted in MEGA4. Statistical support was provided by bootstrapping over 1,000 replicates and bootstrap values >70 are indicated at the correspondent node. The scale bars indicate the estimated numbers of nucleotide substitutions per site. human (Hu), swine (Sw)