Reverse-zoonoses of 2009 H1N1 pandemic influenza A viruses and evolution in United States swine results in viruses with zoonotic potential

Alexey Markin; Giovana Ciacci Zanella; Zebulun W Arendsee; Jianqiang Zhang; Karen M Krueger; Phillip C Gauger; Amy L Vincent Baker; Tavis K Anderson

doi:10.1371/journal.ppat.1011476

Reverse-zoonoses of 2009 H1N1 pandemic influenza A viruses and evolution in United States swine results in viruses with zoonotic potential

PLoS Pathog. 2023 Jul 27;19(7):e1011476. doi: 10.1371/journal.ppat.1011476. eCollection 2023 Jul.

Authors

Alexey Markin^{1

2}, Giovana Ciacci Zanella^{1

3}, Zebulun W Arendsee¹, Jianqiang Zhang², Karen M Krueger², Phillip C Gauger², Amy L Vincent Baker¹, Tavis K Anderson¹

Affiliations

¹ Virus and Prion Research Unit, National Animal Disease Center, United States Department of Agriculture, Agricultural Research Service, Ames, Iowa, United States of America.
² Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, United States of America.
³ Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, United States of America.

Abstract

The 2009 H1N1 pandemic (pdm09) lineage of influenza A virus (IAV) crosses interspecies barriers with frequent human-to-swine spillovers each year. These spillovers reassort and drift within swine populations, leading to genetically and antigenically novel IAV that represent a zoonotic threat. We quantified interspecies transmission of the pdm09 lineage, persistence in swine, and identified how evolution in swine impacted zoonotic risk. Human and swine pdm09 case counts between 2010 and 2020 were correlated and human pdm09 burden and circulation directly impacted the detection of pdm09 in pigs. However, there was a relative absence of pdm09 circulation in humans during the 2020-21 season that was not reflected in swine. During the 2020-21 season, most swine pdm09 detections originated from human-to-swine spillovers from the 2018-19 and 2019-20 seasons that persisted in swine. We identified contemporary swine pdm09 representatives of each persistent spillover and quantified cross-reactivity between human seasonal H1 vaccine strains and the swine strains using a panel of monovalent ferret antisera in hemagglutination inhibition (HI) assays. The swine pdm09s had variable antigenic reactivity to vaccine antisera, but each swine pdm09 clade exhibited significant reduction in cross-reactivity to one or more of the human seasonal vaccine strains. Further supporting zoonotic risk, we showed phylogenetic evidence for 17 swine-to-human transmission events of pdm09 from 2010 to 2021, 11 of which were not previously classified as variants, with each of the zoonotic cases associated with persistent circulation of pdm09 in pigs. These data demonstrate that reverse-zoonoses and evolution of pdm09 in swine results in viruses that are capable of zoonotic transmission and represent a potential pandemic threat.

Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Publication types

Research Support, U.S. Gov't, P.H.S.
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Ferrets
Humans
Immune Sera
Influenza A Virus, H1N1 Subtype* / genetics
Influenza A virus*
Influenza, Human* / epidemiology
Orthomyxoviridae Infections* / epidemiology
Orthomyxoviridae Infections* / veterinary
Phylogeny
Swine
Swine Diseases*
United States / epidemiology
Zoonoses / epidemiology

Substances

Immune Sera

Grants and funding

This work was supported in part by the USDA-ARS (ARS project number 5030-32000-231-000D to ALVB and TKA); USDA-APHIS (ARS project number 5030-32000-231-080-I to ALVB and TKA); the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services (Contract No. 75N93021C00015 to PCG, ALVB, and TKA); the Centers for Disease Control and Prevention (contract number 21FED2100395IPD to ALVB and TKA); the Department of Defense, Defense Advanced Research Projects Agency, Preventing Emerging Pathogenic Threats program (contract number HR00112020034 to PCG, ALVB, and TKA); the USDA-ARS Research Participation Program of the Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy (DOE) and USDA-ARS (contract number DE-AC05-06OR23100 to ZWA); and the SCINet project of the USDA-ARS (ARS project number 0500-00093-001-00-D to ALVB and TKA). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Mention of trade names or commercial products in this article is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the USDA, DOE, CDC, or ORISE. USDA is an equal opportunity provider and employer.