Abstract

An H1N1 subtype influenza A virus with all eight gene segments derived from wild birds (including mallards), ducks and chickens, caused severe disease outbreaks in swine populations in Europe beginning in 1979 and successfully adapted to form the European avian‐like swine (EA‐swine) influenza lineage. Genes of the EA‐swine lineage that are clearly segregated from its closest avian relatives continue to circulate in swine populations globally and represent a unique opportunity to study the adaptive process of an avian‐to‐mammalian cross‐species transmission. Here, we used a relaxed molecular clock model to test whether the EA‐swine virus originated through the introduction of a single avian ancestor as an entire genome, followed by an analysis of host‐specific selection pressures among different gene segments. Our data indicated independent introduction of gene segments via transmission of avian viruses into swine followed by reassortment events that occurred at least 1–4 years prior to the EA‐swine outbreak. All EA‐swine gene segments exhibit greater selection pressure than avian viruses, reflecting both adaptive pressures and relaxed selective constraints that are associated with host switching. Notably, we identified key amino acid mutations in the viral surface proteins (H1 and N1) that play a role in adaptation to new hosts. Following the establishment of EA‐swine lineage, we observed an increased frequency of intrasubtype reassortment of segments compared to the earlier strains that has been associated with adaptive amino acid replacements, disease severity and vaccine escape. Taken together, our study provides key insights into the adaptive changes in viral genomes following the transmission of avian influenza viruses to swine and the early establishment of the EA‐swine lineage.

Highlights

  • Influenza pandemics represent a significant threat to global public health

  • Four major pandemics have been recorded since the 1900s, occurring in 1918, 1957, 1968 and 2009 when influenza A viruses with genes from animal sources adapted to the human population, a process known as antigenic shift (Fraser et al, 2009; Garten et al, 2009; Kilbourne, 2006; Smith, Vijaykrishna, et al, 2009; Taubenberger, Hultin, & Morens, 2007; Webster, Bean, Gorman, Chambers, & Kawaoka, 1992)

  • 1930s has shown that the H2N2/1957 and H3N2/1968 pandemic viruses resulted from reassortment of animal and circulating human viruses (Kawaoka, Krauss, & Webster, 1989; Schäffr et al, 1993; Scholtissek, Rohde, Von Hoyningen, & Rott, 1978)

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Summary

| INTRODUCTION

Influenza pandemics represent a significant threat to global public health. Four major pandemics have been recorded since the 1900s, occurring in 1918, 1957, 1968 and 2009 when influenza A viruses with genes from animal sources adapted to the human population, a process known as antigenic shift (Fraser et al, 2009; Garten et al, 2009; Kilbourne, 2006; Smith, Vijaykrishna, et al, 2009; Taubenberger, Hultin, & Morens, 2007; Webster, Bean, Gorman, Chambers, & Kawaoka, 1992). Evolutionary analysis (Worobey et al, 2014) indicated that the CS HA-­H1 lineage directly descended from the human pandemic 1918 virus to form a stable lineage that has circulated for at least 80 years in swine Reassortment of this lineage was first observed in 1998, when several severe outbreaks occurred in pig farms across North America (Webby et al, 2000; Zhou et al, 1999). These outbreaks were caused by the emergence of two distinctive H3N2 viruses: a double-­reassortant that contained CS H1N1 and human H3N2 virus genes, and a virus that contained the triple-­reassortant internal gene cassette (TRIG) that incorporated additional avian gene segments. Identifying the key changes in cross-­ species transmission will provide insight into the potential genetic factors that may be responsible for host adaptation and gain understanding into the patterns of adaptive evolution in establishing stable lineage descendants

| MATERIALS AND METHODS
| DISCUSSION
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