Adaptation of Human Influenza Viruses to Swine

Abstract

A large diversity of influenza A viruses (IAV) within the H1N1/N2 and H3N2 subtypes circulates in pigs globally, with different lineages predominating in specific regions of the globe. A common characteristic of the ecology of IAV in swine in different regions is the periodic spillover of human seasonal viruses. Such human viruses resulted in sustained transmission in swine in several countries, leading to the establishment of novel IAV lineages in the swine host and contributing to the genetic and antigenic diversity of influenza observed in pigs. In this review we discuss the frequent occurrence of reverse-zoonosis of IAV from humans to pigs that have contributed to the global viral diversity in swine in a continuous manner, describe host-range factors that may be related to the adaptation of these human-origin viruses to pigs, and how these events could affect the swine industry.

Keywords: adaptation; host range; human; influenza A virus; interspecies; swine.

Figure 1

Overall distribution of α2,6-linked sialic acid (SA; green long arrow) and α2,3-linked SA (blue short arrow) in the epithelium of the respiratory tract of pigs (18, 19) and humans (14, 15). Adapted from de Graaf and Fouchier (20).

Figure 2

Host range determinants of influenza A viruses (IAV). (A) Avian influenza virus HA protein recognize short α2,3-linked sialic acid (blue), whereas HA from human and swine IAV recognize long α2,6-linked sialic acid (green). (B) The balance between the HA binding affinity and the NA activity to cleave sialic acid receptors is important for replication and adaptation to a new species. If a virus has strong biding affinity but low cleavage activity replication may be reduced. (C) The PB2 polymerase has an impact in the optimal replication temperature of IAV and can restrict host range. K627 increases replication at the low temperature of human or swine upper airway. E627 decreases replication at low temperatures, unless in combination with A271 or N701. (D) The sensitivity of a virus to host-specific innate immune factors can restrict interspecies transmission of IAV. To be able to replicate and spread in a new host, IAV must become resistant to the antiviral activity of interferon-induced Mx protein or to the neutralizing activity of surfactant protein D (SP-D) from that particular host. Adapted from Cauldwell et al. (39).

Figure 3

Proportion of amino acids found in influenza A viruses circulating in pigs globally at the HA receptor-binding site positions previously shown to impact receptor-specificity for H1, H3, and H9. Analysis was performed using the Influenza Research Database Sequence Variation (SNP) tool (44). Sequences with 100% identity were removed resulting in a set of 8076 H1 HA, 2287 H3 HA, and 46 H9 HA swine IAV sequences. The amino acids previously shown to change receptor-binding specificity are displayed on the right.

Figure 4

Different subtypes/lineages of human-origin influenza viruses circulating in swine in different continents. The map is colored according to pork production in 1,000 metric tons. Map created with mapchart.net.