Regional patterns of genetic diversity in swine influenza A viruses in the United States from 2010 to 2016

ABSTRACT Repeated spillovers of the H1N1 pandemic virus (H1N1pdm09) from humans to pigs resulted in substantial evolution of influenza A viruses infecting swine, contributing to the genetic and antigenic diversity of influenza A viruses (IAV) currently circulating in swine. The reassortment with endemic swine viruses and maintenance of some of the H1N1pdm09 internal genes resulted in the circulation of different genomic constellations in pigs. Here, we performed a whole-genome phylogenetic analysis of 368 IAV circulating in swine from 2009 to 2016 in the United States. We identified 44 different genotypes, with the most common genotype (32.33%) containing a clade IV-A HA gene, a 2002-lineage NA gene, an M-pdm09 gene, and remaining gene segments of triple reassortant internal gene (TRIG) origin. To understand how different genetic constellations may relate to viral fitness, we compared the pathogenesis and transmission in pigs of six representative genotypes. Although all six genotypes efficiently infected pigs, they resulted in different degrees of pathology and viral shedding. These results highlight the vast H3N2 genetic diversity circulating in U.S. swine after 2009. This diversity has important implications in the control of this disease by the swine industry, as well as a potential risk for public health if swine-adapted viruses with H1N1pdm09 genes have an increased risk to humans, as occurred in the 2011-2012 and 2016 human variant H3N2v cases associated with exhibition swine. IMPORTANCE People continue to spread the 2009 H1N1 pandemic (H1N1pdm09) IAV to pigs, allowing H1N1pdm09 to reassort with endemic swine IAV. In this study, we determined the 8 gene combinations of swine H3N2 IAV detected from 2009 to 2016. We identified 44 different genotypes of H3N2, the majority of which contained at least one H1N1pdm09 gene segment. We compared six representative genotypes of H3N2 in pigs. All six genotypes efficiently infected pigs, but they resulted in different degrees of lung damage and viral shedding. These results highlight the vast genetic diversity of H3N2 circulating in U.S. swine after 2009, with important implications for the control of IAV for the swine industry. Because H1N1pdm09 is also highly adapted to humans, these swine viruses pose a potential risk to public health if swine-adapted viruses with H1N1pdm09 genes also have an increased risk for human infection.

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Feral Swine in the United States Have Been Exposed to both Avian and Swine Influenza A Viruses

Applied and Environmental Microbiology ◽

10.1128/aem.01346-17 ◽

2017 ◽

Vol 83 (19) ◽

Cited By ~ 13

Author(s):

Brigitte E. Martin ◽

Hailiang Sun ◽

Margaret Carrel ◽

Fred L. Cunningham ◽

John A. Baroch ◽

...

Keyword(s):

United States ◽

Influenza A ◽

Swine Influenza ◽

The United States ◽

Wild Birds ◽

Influenza A Viruses ◽

Serum Samples ◽

Feral Swine ◽

Free Ranging ◽

Domestic Swine

ABSTRACT Influenza A viruses (IAVs) in swine can cause sporadic infections and pandemic outbreaks among humans, but how avian IAV emerges in swine is still unclear. Unlike domestic swine, feral swine are free ranging and have many opportunities for IAV exposure through contacts with various habitats and animals, including migratory waterfowl, a natural reservoir for IAVs. During the period from 2010 to 2013, 8,239 serum samples were collected from feral swine across 35 U.S. states and tested against 45 contemporary antigenic variants of avian, swine, and human IAVs; of these, 406 (4.9%) samples were IAV antibody positive. Among 294 serum samples selected for antigenic characterization, 271 cross-reacted with ≥1 tested virus, whereas the other 23 did not cross-react with any tested virus. Of the 271 IAV-positive samples, 236 cross-reacted with swine IAVs, 1 with avian IAVs, and 16 with avian and swine IAVs, indicating that feral swine had been exposed to both swine and avian IAVs but predominantly to swine IAVs. Our findings suggest that feral swine could potentially be infected with both avian and swine IAVs, generating novel IAVs by hosting and reassorting IAVs from wild birds and domestic swine and facilitating adaptation of avian IAVs to other hosts, including humans, before their spillover. Continued surveillance to monitor the distribution and antigenic diversities of IAVs in feral swine is necessary to increase our understanding of the natural history of IAVs. IMPORTANCE There are more than 5 million feral swine distributed across at least 35 states in the United States. In contrast to domestic swine, feral swine are free ranging and have unique opportunities for contact with wildlife, livestock, and their habitats. Our serological results indicate that feral swine in the United States have been exposed to influenza A viruses (IAVs) consistent with those found in both domestic swine and wild birds, with the predominant infections consisting of swine-adapted IAVs. Our findings suggest that feral swine have been infected with IAVs at low levels and could serve as hosts for the generation of novel IAVs at the interface of feral swine, wild birds, domestic swine, and humans.

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Evolution and antigenic advancement of N2 neuraminidase of swine influenza A viruses circulating in the United States following two separate introductions from human seasonal viruses

Journal of Virology ◽

10.1128/jvi.00632-21 ◽

2021 ◽

Author(s):

Bryan S. Kaplan ◽

Tavis K. Anderson ◽

Jennifer Chang ◽

Jefferson Santos ◽

Daniel Perez ◽

...

Keyword(s):

United States ◽

Influenza A Virus ◽

Influenza A ◽

Vaccine Development ◽

Swine Influenza ◽

The United States ◽

Antigenic Drift ◽

Effective Control ◽

Influenza A Viruses ◽

Antigenic Diversity

Two separate introductions of human seasonal N2 neuraminidase genes were sustained in United States swine since 1998 (N2-98) and 2002 (N2-02). Herein, we characterized the antigenic evolution of the N2 of swine influenza A virus (IAV) across two decades following each introduction. The N2-98 and N2-02 expanded in genetic diversity, with two statistically supported monophyletic clades within each lineage. To assess antigenic drift in swine N2 following the human-to-swine spillover events, we generated a panel of swine N2 antisera against representative N2 and quantified the antigenic distance between wild-type viruses using enzyme-linked lectin assay and antigenic cartography. The antigenic distance between swine and human N2 was smallest between human N2 circulating at the time of each introduction and the archetypal swine N2. However, sustained circulation and evolution in swine of the two N2 lineages resulted in significant antigenic drift, and the N2-98 and N2-02 swine N2 lineages were antigenically distinct. Although intra-lineage antigenic diversity was observed, the magnitude of antigenic drift did not consistently correlate with the observed genetic differences. These data represent the first quantification of the antigenic diversity of neuraminidase of IAV in swine and demonstrated significant antigenic drift from contemporary human seasonal strains as well as antigenic variation among N2 detected in swine. These data suggest that antigenic mismatch may occur between circulating swine IAV and vaccine strains. Consequently, consideration of the diversity of N2 in swine IAV for vaccine selection may likely result in more effective control, and aid public health initiatives for pandemic preparedness. Importance Antibodies inhibiting the neuraminidase (NA) of influenza A virus (IAV) reduce clinical disease, virus shedding, and transmission, particularly in the absence of neutralizing immunity against the hemagglutinin. To understand antibody recognition of the genetically diverse NA in U.S. swine IAV, we characterized the antigenic diversity of N2 from swine and humans. N2 detected in swine IAV were derived from two distinct human-to-swine spillovers that persisted, are antigenically distinct, and underwent antigenic drift. These findings highlight the need for continued surveillance and vaccine development in swine with increased focus on the NA. Additionally, human seasonal N2 isolated after 2005 were poorly inhibited by representative swine N2 antisera, suggesting a lack of cross-reactive NA antibody mediated immunity between contemporary swine and human N2. Bidirectional transmission between humans and swine represents a One Health challenge, and determining the correlates of immunity to emerging IAV strains is critical to mitigate zoonotic and reverse-zoonotic transmission.

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Antigenic evolution of H3N2 influenza A viruses in swine in the United States from 2012 to 2016

Influenza and Other Respiratory Viruses ◽

10.1111/irv.12610 ◽

2018 ◽

Vol 13 (1) ◽

pp. 83-90 ◽

Cited By ~ 9

Author(s):

Marcus J. Bolton ◽

Eugenio J. Abente ◽

Divya Venkatesh ◽

Jered A. Stratton ◽

Michael Zeller ◽

...

Keyword(s):

United States ◽

Influenza A ◽

The United States ◽

Influenza A Viruses ◽

Antigenic Evolution ◽

H3n2 Influenza

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Introduction, Evolution, and Dissemination of Influenza A Viruses in Exhibition Swine in the United States during 2009 to 2013

Journal of Virology ◽

10.1128/jvi.01457-16 ◽

2016 ◽

Vol 90 (23) ◽

pp. 10963-10971 ◽

Cited By ~ 11

Author(s):

Martha I. Nelson ◽

Karla M. Stucker ◽

Seth A. Schobel ◽

Nídia S. Trovão ◽

Suman R. Das ◽

...

Keyword(s):

United States ◽

Population Dynamics ◽

Influenza A Virus ◽

Influenza A ◽

The United States ◽

Viral Population ◽

Influenza A Viruses ◽

Swine Industry ◽

Virus Diversity ◽

Agricultural Fairs

ABSTRACT The swine-human interface created at agricultural fairs, along with the generation of and maintenance of influenza A virus diversity in exhibition swine, presents an ongoing threat to public health. Nucleotide sequences of influenza A virus isolates collected from exhibition swine in Ohio ( n = 262) and Indiana ( n = 103) during 2009 to 2013 were used to investigate viral evolution and movement within this niche sector of the swine industry. Phylogenetic and Bayesian analyses were employed to identify introductions of influenza A virus to exhibition swine and study viral population dynamics. In 2013 alone, we identified 10 independent introductions of influenza A virus into Ohio and/or Indiana exhibition swine. Frequently, viruses from the same introduction were identified at multiple fairs within the region, providing evidence of rapid and widespread viral movement within the exhibition swine populations of the two states. While pigs moving from fair to fair to fair is possible in some locations, the concurrent detection of nearly identical strains at several fairs indicates that a common viral source was more likely. Importantly, we detected an association between the high number of human variant H3N2 (H3N2v) virus infections in 2012 and the widespread circulation of influenza A viruses of the same genotype in exhibition swine in Ohio fairs sampled that year. The extent of viral diversity observed in exhibition swine and the rapidity with which it disseminated across long distances indicate that novel strains of influenza A virus will continue to emerge and spread within exhibition swine populations, presenting an ongoing threat to humans. IMPORTANCE Understanding the underlying population dynamics of influenza A viruses in commercial and exhibition swine is central to assessing the risk for human infections with variant viruses, including H3N2v. We used viral genomic sequences from isolates collected from exhibition swine during 2009 to 2013 to understand how the peak of H3N2v cases in 2012 relates to long-term trends in the population dynamics of pandemic viruses recently introduced into commercial and exhibition swine in the United States. The results of our spatial analysis underscore the key role of rapid viral dispersal in spreading multiple genetic lineages throughout a multistate network of agricultural fairs, providing opportunities for divergent lineages to coinfect, reassort, and generate new viral genotypes. The higher genetic diversity of genotypes cocirculating in exhibition swine since 2013 could facilitate the evolution of new reassortants, potentially with even greater ability to cause severe infections in humans or cause human-to-human transmission, highlighting the need for continued vigilance.

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Interspecies Transmission and Reassortment of Influenza A Viruses in Pigs and Turkeys in the United States

American Journal of Epidemiology ◽

10.1093/oxfordjournals.aje.a116522 ◽

1992 ◽

Vol 136 (4) ◽

pp. 488-497 ◽

Cited By ~ 47

Author(s):

Stephen M. Wright ◽

Yoshihiro Kawaoka ◽

Gerold B. Sharp ◽

Dennis A. Senne ◽

Robert G. Webster

Keyword(s):

United States ◽

Influenza A ◽

The United States ◽

Interspecies Transmission ◽

Influenza A Viruses

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Genetic Characterization of H1N2 Influenza A Viruses Isolated from Pigs throughout the United States

Journal of Clinical Microbiology ◽

10.1128/jcm.40.3.1073-1079.2002 ◽

2002 ◽

Vol 40 (3) ◽

pp. 1073-1079 ◽

Cited By ~ 93

Author(s):

A. I. Karasin ◽

J. Landgraf ◽

S. Swenson ◽

G. Erickson ◽

S. Goyal ◽

...

Keyword(s):

United States ◽

Influenza A ◽

Genetic Characterization ◽

The United States ◽

Influenza A Viruses

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The enigma of the apparent disappearance of Eurasian highly pathogenic H5 clade 2.3.4.4 influenza A viruses in North American waterfowl

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1608853113 ◽

2016 ◽

Vol 113 (32) ◽

pp. 9033-9038 ◽

Cited By ~ 37

Author(s):

Scott Krauss ◽

David E. Stallknecht ◽

Richard D. Slemons ◽

Andrew S. Bowman ◽

Rebecca L. Poulson ◽

...

Keyword(s):

United States ◽

North America ◽

North American ◽

Influenza A ◽

Wild Bird ◽

Animal Health ◽

The United States ◽

Influenza Viruses ◽

Influenza A Viruses ◽

Highly Pathogenic

One of the major unresolved questions in influenza A virus (IAV) ecology is exemplified by the apparent disappearance of highly pathogenic (HP) H5N1, H5N2, and H5N8 (H5Nx) viruses containing the Eurasian hemagglutinin 2.3.4.4 clade from wild bird populations in North America. The introduction of Eurasian lineage HP H5 clade 2.3.4.4 H5N8 IAV and subsequent reassortment with low-pathogenic H?N2 and H?N1 North American wild bird-origin IAVs in late 2014 resulted in widespread HP H5Nx IAV infections and outbreaks in poultry and wild birds across two-thirds of North America starting in November 2014 and continuing through June 2015. Although the stamping out strategies adopted by the poultry industry and animal health authorities in Canada and the United States—which included culling, quarantining, increased biosecurity, and abstention from vaccine use—were successful in eradicating the HP H5Nx viruses from poultry, these activities do not explain the apparent disappearance of these viruses from migratory waterfowl. Here we examine current and historical aquatic bird IAV surveillance and outbreaks of HP H5Nx in poultry in the United States and Canada, providing additional evidence of unresolved mechanisms that restrict the emergence and perpetuation of HP avian influenza viruses in these natural reservoirs.

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