Novel Reassortant Human-Like H3N2 and H3N1 Influenza A Viruses Detected in Pigs Are Virulent and Antigenically Distinct from Swine Viruses Endemic to the United States

Abstract

Human-like swine H3 influenza A viruses (IAV) were detected by the USDA surveillance system. We characterized two novel swine human-like H3N2 and H3N1 viruses with hemagglutinin (HA) genes similar to those in human seasonal H3 strains and internal genes closely related to those of 2009 H1N1 pandemic viruses. The H3N2 neuraminidase (NA) was of the contemporary human N2 lineage, while the H3N1 NA was of the classical swine N1 lineage. Both viruses were antigenically distant from swine H3 viruses that circulate in the United States and from swine vaccine strains and also showed antigenic drift from human seasonal H3N2 viruses. Their pathogenicity and transmission in pigs were compared to those of a human H3N2 virus with a common HA ancestry. Both swine human-like H3 viruses efficiently infected pigs and were transmitted to indirect contacts, whereas the human H3N2 virus did so much less efficiently. To evaluate the role of genes from the swine isolates in their pathogenesis, reverse genetics-generated reassortants between the swine human-like H3N1 virus and the seasonal human H3N2 virus were tested in pigs. The contribution of the gene segments to virulence was complex, with the swine HA and internal genes showing effects in vivo. The experimental infections indicate that these novel H3 viruses are virulent and can sustain onward transmission in pigs, and the naturally occurring mutations in the HA were associated with antigenic divergence from H3 IAV from humans and swine. Consequently, these viruses could have a significant impact on the swine industry if they were to cause more widespread outbreaks, and the potential risk of these emerging swine IAV to humans should be considered. IMPORTANCE Pigs are important hosts in the evolution of influenza A viruses (IAV). Human-to-swine transmissions of IAV have resulted in the circulation of reassortant viruses containing human-origin genes in pigs, greatly contributing to the diversity of IAV in swine worldwide. New human-like H3N2 and H3N1 viruses that contain a mix of human and swine gene segments were recently detected by the USDA surveillance system. The human-like viruses efficiently infected pigs and resulted in onward airborne transmission, likely due to the multiple changes identified between human and swine H3 viruses. The human-like swine viruses are distinct from contemporary U.S. H3 swine viruses and from the strains used in swine vaccines, which could have a significant impact on the swine industry due to a lack of population immunity. Additionally, public health experts should consider an appropriate assessment of the risk of these emerging swine H3 viruses for the human population.

The genomic evolution of H1 influenza A viruses from swine detected in the United States between 2009 and 2016

“…Previous papers demonstrated that antigenic evolution was associated with reassortment [6,18,21,22] and here we observed an increase in HA diversity concurrent with reassortment between the endemic H1 lineages and the H1N1pdm09. Vaccines against IAV are routinely used in swine in the US; however, the continued presence of such a diverse population of swine H1 IAV may limit the effectiveness of these vaccines [19,[31][32][33].…”

“…In this study, we identified the genome patterns of H1N1 and H1N2 collected from swine in the United States from 2009 to 2016. Similar studies with H3N2 viruses from US swine populations have been previously reported [6,23], but a comprehensive analysis of H1 IAV was lacking. Among the 616 unique genome sets for H1N1 and H1N2 viruses, 74 whole-genome patterns and 47 NA+internal patterns were identified.…”

“…The diversity of IAV observed in swine populations is the result of the introduction of novel strains from other hosts, primarily humans, and reassortment with endemic viruses [5,6]. Consequently, each of the eight genes of swine IAV may be attributed to lineages based on avian, human, or swine origin.…”

Origin, distribution, and potential risk factors associated with influenza A virus in swine in two production systems in Guatemala

“…In this tree, the swine isolate from Guatemala still clustered in a separate clade from the vaccine lineages but with viruses from other geographic regions, indicating that the circulation of viruses from this clade was not exclusive to Central America. Inclusion of HA sequences of recent human‐like swine isolates 26 revealed that viruses from the same clade as the 040078‐H3N2 have been recently introduced in pigs in the United States.…”

“…The mutations in the HA1 protein of 040078‐H3N2 in comparison with the vaccine strains suggest differences in antigenicity with other viruses of human origin. Significant antigenic distance was shown for recent swine isolates from the same genetic cluster,26 meaning that even when other H3 viruses already circulate in pigs in Guatemala, there could be little cross‐protection to a virus like the 040078‐H3N2. Experimental evaluation of the transmissibility of this virus in pigs could help assess the risk of onward transmission in this host.…”