Substantial Antigenic Drift in the Hemagglutinin Protein of Swine Influenza A Viruses

Abstract

The degree of antigenic drift in swine influenza A viruses (swIAV) has historically been regarded as minimal compared to that of human influenza A virus strains. However, as surveillance activities on swIAV have increased, more isolates have been characterized, revealing a high level of genetic and antigenic differences even within the same swIAV lineage. The objective of this study was to investigate the level of genetic drift in one enzootically infected swine herd over one year. Nasal swabs were collected monthly from sows (n = 4) and piglets (n = 40) in the farrowing unit, and from weaners (n = 20) in the nursery. Virus from 1–4 animals were sequenced per month. Analyses of the sequences revealed that the hemagglutinin (HA) gene was the main target for genetic drift with a substitution rate of 7.6 × 10−3 substitutions/site/year and evidence of positive selection. The majority of the mutations occurred in the globular head of the HA protein and in antigenic sites. The phylogenetic tree of the HA sequences displayed a pectinate typology, where only a single lineage persists and forms the ancestor for subsequent lineages. This was most likely caused by repeated selection of a single immune-escape variant, which subsequently became the founder of the next wave of infections.

Co-circulation of multiple influenza A variants in swine harboring genes from seasonal human and swine influenza viruses

“…IAV infections in swine has been considered a disease of late autumn and early winter [30][31][32][33] , but the results reported here reveal that while the percentage of samples testing positive for swIAV fluctuate between months, no significant differences are observed between the different seasons. This supports the recent studies describing the enzootic persistence of swIAV [34][35][36][37] , most likely as a consequence of the herd-sizes and management procedures under the current conditions of commercial swine herds. A similar lack of seasonality was found in other countries with comparable management structures 16,33,38 .…”

“…Finally, the substitution rate estimated for H1av was similar to that documented in previous studies [52][53][54][55] , but was lower than the substitution rate estimated for H1av in a single herd over time 37 . This emphasize that one should differentiate when comparing evolutionary results based on data obtained from a single herd or data obtained through extensive surveillance programs.…”

“…It was evident that the evolution of the H1av gene did not evolve in one specific direction over time, but rather evolved in many different directions, resulting in a vast number of different H1av clusters and variants. In a recent study 37 , we found that the evolution of the H1av in a single herd followed a pectinate pattern mirroring the pattern seen globally for the human seasonal influenza strains, which contradict the general perception that swine IAV is not prone to selection driven by preexisting immunity like in humans. In the present study, we assessed the H1av evolution over time in the Danish pig population as a whole and over several years and failed to confirm this pectinate pattern.…”

Evaluation of the Pathogenicity and the Escape from Vaccine Protection of a New Antigenic Variant Derived from the European Human-Like Reassortant Swine H1N2 Influenza Virus

“…Strains that are included in swine influenza vaccine are rarely updated [ 28 ], since antigenic drift of influenza A viruses has been considered to be much slower in swine than in human [ 35 ]. However, in recent years, the diversity of antigenic variant swIAV has been steadily increasing in pigs, because of antigenic shift or drift [ 36 , 37 , 38 ]. Thus, the question of updating the vaccine antigens and/or change the vaccine strategy (e.g., live attenuated influenza virus vaccine) to better adapt to the field situations can arise.…”

A universal RT-qPCR assay for “One Health” detection of influenza A viruses

“…In addition, a more recently designed RT-qPCR which amplifies elsewhere within the MP-segment was validated [24] and featured successfully in subsequent AIV outbreaks and wild bird investigations [25][26][27][28], AIV in vivo studies [29,30] and SwIV field investigations [31][32][33][34]. The importance of appropriate test validation has been emphasised in a veterinary context [35], with an MP-segment RT-qPCR for generic detection of contemporary H1N1, H1N2 and H3N2 SwIV subtypes in European pigs having been also validated [36].…”