Literature detail

Characterization of a 2016-2017 Human Seasonal H3 Influenza A Virus Spillover Now Endemic to U.S. Swine.

Aditi Sharma¹ Michael A Zeller¹ Carine K Souza² Tavis K Anderson² Amy L Vincent² Karen Harmon¹ Ganwu Li¹ Jianqiang Zhang¹ Phillip C Gauger¹

Affiliations 2 institutions

Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State Universitygrid.34421.30, Ames, Iowa, USA.
Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS, Ames, Iowa, USA.

PMID 35019669 2022 mSphere eng ppublish

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Article

Publication summary

In 2017, the Iowa State University Veterinary Diagnostic Laboratory detected a reverse-zoonotic transmission of a human seasonal H3 influenza A virus into swine (IAV-S) in Oklahoma. Pairwise comparison between the recently characterized human seasonal H3 IAV-S (H3.2010.2) hemagglutinin (HA) sequences detected in swine and the most similar 2016-2017 human seasonal H3 revealed 99.9% nucleotide identity. To elucidate the origin of H3.2010.2 IAV-S, 45 HA and 27 neuraminidase (NA) sequences from 2017 to 2020 as well as 11 whole-genome sequences (WGS) were genetically characterized. Time to most recent common human ancestor was estimated between August and September 2016. The N2 NA was of human origin in all but one strain from diagnostic submissions with NA sequences, and the internal gene segments from WGS consisted of matrix genes originating from the 2009 pandemic H1N1 and another 5 internal genes of triple reassortant swine origin (TTTTPT). Pigs experimentally infected with H3.2010.2 demonstrated efficient nasal shedding and replication in the lungs, mild pneumonia, and minimal microscopic lung lesions and transmitted the virus to indirect contact swine. Antigenically, H3.2010.2 viruses were closer to a human seasonal vaccine strain, A/Hong Kong/4801/2014, than to the H3.2010.1 human seasonal H3 viruses detected in swine in 2012. This was the second sustained transmission of a human seasonal IAV into swine from the 2010 decade after H3.2010.1. Monitoring the spillover and detection of novel IAV from humans to swine may help vaccine antigen selection and could impact pandemic preparedness. <b>IMPORTANCE</b> H3.2010.2 is a new phylogenetic clade of H3N2 circulating in swine that became established after the spillover of a human seasonal H3N2 from the 2016-2017 influenza season. The novel H3.2010.2 transmitted and adapted to the swine host and demonstrated reassortment with internal genes from strains endemic to pigs, but it maintained human-like HA and NA. It is genetically and antigenically distinct from the H3.2010.1 H3N2 introduced earlier in the 2010 decade. Human seasonal IAV spillovers into swine become established in the population through adaptation and sustained transmission and contribute to the genetic and antigenic diversity of IAV circulating in swine. Continued IAV surveillance is necessary to detect emergence of novel strains in swine and assist with vaccine antigen selection to improve the ability to prevent respiratory disease in swine as well as the risk of zoonotic transmission.

H3.2010.2 H3N2 human-to-swine spillover influenza A virus reverse zoonosis swine Influenza A Virus, H3N2 Subtype Orthomyxoviridae Infections Swine Diseases Animals Humans Influenza A Virus, H1N1 Subtype Neuraminidase Phylogeny Seasons Swine Vaccines

Structured evidence records

Evidence records

6 total

Genomic Evolution 1 records

Genomic Evolution Extraction confidence 0.90

Key finding

Genetic and phylogenetic analyses of HA, NA, and whole-genome sequences showed that H3.2010.2 originated from a 2016–2017 human seasonal H3N2 strain and subsequently adapted and reassorted in swine.

Virus

Host

Location

Supporting text

Pairwise comparison between the recently characterized human seasonal H3 IAV-S (H3.2010.2) hemagglutinin (HA) sequences detected in swine and the most similar 2016-2017 human seasonal H3 revealed 99.9% nucleotide identity. To elucidate the origin of H3.2010.2 IAV-S, 45 HA and 27 neuraminidase (NA) sequences from 2017 to 2020 as well as 11 whole-genome sequences (WGS) were genetically characterized. Time to most recent common human ancestor was estimated between August and September 2016.

Genes or proteins: HA; NA; matrix; internal gene segments
Analysis methods: pairwise sequence comparison; phylogenetic analysis; genetic characterization

Host Range Experiment 1 records

Host Range Experiment Extraction confidence 0.90

Key finding

Experimental infection demonstrated that H3.2010.2 replicated efficiently in pigs and was transmissible to indirect contact swine.

Virus

Host

Location

Supporting text

Pigs experimentally infected with H3.2010.2 demonstrated efficient nasal shedding and replication in the lungs, mild pneumonia, and minimal microscopic lung lesions and transmitted the virus to indirect contact swine.

Method: experimental infection
Sample type: nasal secretions; lungs
Experimental system: in vivo animal experiment

Molecular Adaptation 1 records

Molecular Adaptation Extraction confidence 0.85

Key finding

Human seasonal H3N2 virus clade H3.2010.2 adapted to swine after reverse zoonosis, maintaining human-origin HA and NA but reassorting internal genes from endemic swine strains, supporting molecular adaptation to the swine host.

Virus

Host

Location

Supporting text

The novel H3.2010.2 transmitted and adapted to the swine host and demonstrated reassortment with internal genes from strains endemic to pigs, but it maintained human-like HA and NA.

Genes or proteins: HA; NA
Mechanism types: host_adaptation; reassortment; replication_efficiency; transmission_fitness

Recombination Or Reassortment 1 records

Recombination Or Reassortment Extraction confidence 0.88

Key finding

H3.2010.2 influenza A virus was a reassortant carrying human-origin HA and NA genes and internal gene segments derived from swine viruses and pandemic H1N1, illustrating reassortment following human-to-swine spillover.

Virus

Host

Location

Supporting text

The novel H3.2010.2 transmitted and adapted to the swine host and demonstrated reassortment with internal genes from strains endemic to pigs, but it maintained human-like HA and NA.

Event type: reassortment
Genes or segments: HA; NA; matrix gene; internal gene segments

Spillover Event 1 records

Spillover Event Extraction confidence 0.98

Key finding

A human seasonal H3 influenza A virus spilled over from humans to swine in Oklahoma in 2017, establishing a new lineage now circulating in U.S. swine.

Virus

Host

Location

Supporting text

In 2017, the Iowa State University Veterinary Diagnostic Laboratory detected a reverse-zoonotic transmission of a human seasonal H3 influenza A virus into swine (IAV-S) in Oklahoma.

Method: sequencing; phylogenetic analysis; experimental infection
Study design: outbreak investigation
Transmission direction: human-to-animal
Geographic raw: Oklahoma
Country inferred: United States

Zoonotic Surveillance 1 records

Zoonotic Surveillance Extraction confidence 0.90

Key finding

Surveillance detected a human-origin H3N2 influenza A virus lineage in swine in Oklahoma, indicating ongoing monitoring of IAV in U.S. swine populations.

Virus

Host

Location

Supporting text

Method: viral detection; genetic characterization
Geographic raw: Oklahoma
Country inferred: United States

Citation context

References

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PMID 30210800	2018. The continual threat of influenza virus infections at the human-animal interface: what is new from a one health perspective? Evol Med Public Health 2018:192–198	Bailey	2018
PMID 30723723	2018. Adaptation of human influenza viruses to swine. Front Vet Sci 5:347	Rajao	2018
PMID 31661057	2020. Locally acquired human infection with swine-origin influenza A(H3N2) variant virus, Australia, 2018	Deng	2018
-	1990. Pigs as “mixing vessels” for the creation of new pandemic influenza A viruses. Med Princ Pract 2:65–71	Scholtissek	1990
PMID 11875246	2002. Updating the accounts: global mortality of the 1918–1920 “Spanish” influenza pandemic. Bull Hist Med 76:105–115	Johnson	2002
PMID 22696653	2012. Evolution of novel reassortant A/H3N2 influenza viruses in North American swine and humans, 2009–2011	Nelson	2011
PMID 21892996	2011. Multiple reassortment between pandemic (H1N1) 2009 and endemic influenza viruses in pigs, United States	Ducatez	2009
PMID 31988203	2021. Swine influenza A viruses and the tangled relationship with humans. Cold Spring Harb Perspect Med 11:a038737	Anderson	2021
PMID 24965467	2014. Introductions and evolution of human-origin seasonal influenza a viruses in multinational swine populations	Nelson	2014
PMID 25564096	2015. Reverse zoonosis of influenza to swine: new perspectives on the human-animal interface. Trends Microbiol 23:142–153	Nelson	2014
PMID 29109276	2017. Contemporary H3N2 influenza viruses have a glycosylation site that alters binding of antibodies elicited by egg-adapted vaccine strains	Zost	2017
PMID 28758634	2017. The genomic evolution of H1 influenza A viruses from swine detected in the United States between 2009 and 2016	Gao	2010
PMID 26311895	2015. 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	Rajão	2015
PMID 31395641	2019. octoFLU: automated classification for the evolutionary origin of influenza a virus gene sequences detected in U.S. swine. Microbiol Resour Announc 8:e00673-19	Chang	2019
PMID 30382842	2018. ISU FLUture: a veterinary diagnostic laboratory web-based platform to monitor the temporal genetic patterns of influenza A virus in swine. BMC Bioinformatics 19:397	Zeller	2018
PMID 29624873	2019. Regional patterns of genetic diversity in swine influenza A viruses in the United States from 2010 to 2016. Influenza Other Respir Viruses 13:262–273	Walia	2016
PMID 24522915	2014. Substitutions near the hemagglutinin receptor-binding site determine the antigenic evolution of influenza A H3N2 viruses in U.S. swine	Lewis	2014
PMID 22791604	2012. Global transmission of influenza viruses from humans to swine	Nelson	2012
PMID 15163491	2004. Multiple lineages of antigenically and genetically diverse influenza A virus co-circulate in the United States swine population	Webby	2004
PMID 10482643	1999. Genetic reassortment of avian, swine, and human influenza A viruses in American pigs	Zhou	1999
PMID 10954521	2000. Evolution of swine H3N2 influenza viruses in the United States	Webby	2000
PMID 30216671	2019. Antigenic evolution of H3N2 influenza A viruses in swine in the United States from 2012 to 2016. Influenza Other Respir Viruses 13:83–90	Bolton	2016
PMID 11987141	2002. Functional balance between haemagglutinin and neuraminidase in influenza virus infections. Rev Med Virol 12:159–166	Wagner	2002
PMID 19119420	2009. Transmission of influenza virus in a mammalian host is increased by PB2 amino acids 627K or 627E/701N	Steel	2009
PMID 21880744	2011. The M segment of the 2009 new pandemic H1N1 influenza virus is critical for its high transmission efficiency in the guinea pig model	Chou	2009
PMID 27928015	2017. Reassortment between swine H3N2 and 2009 pandemic H1N1 in the United States resulted in influenza A viruses with diverse genetic constellations with variable virulence in pigs	Rajão	2009
PMID 30730827	2019. Human-origin influenza A(H3N2) reassortant viruses in swine, southeast Mexico	Nelson	2019
PMID 27384658	2016. The molecular determinants of antibody recognition and antigenic drift in the H3 hemagglutinin of swine influenza A virus	Abente	2016
PMID 23498956	2013. Defining influenza A virus hemagglutinin antigenic drift by sequential monoclonal antibody selection	Das	2013
PMID 30940704	2019. Human influenza A virus hemagglutinin glycan evolution follows a temporal pattern to a glycan limit. mBio 10:e00204-19	Altman	2019
PMID 28820376	2017. Influenza A(H3N2) virus in swine at agricultural fairs and transmission to humans, Michigan and Ohio, USA, 2016	Bowman	2016
PMID 30359341	2018. Influenza A(H3N2) variant virus outbreak at three fairs–Maryland, 2017. MMWR Morb Mortal Wkly Rep 67:1169–1173	Duwell	2017
-	1938. A simple method of estimating fifty per cent endpoints. Am J Epidemiol 27:493–497	Reed	1938
PMID 29801460	2018. Metagenomic analysis of the RNA fraction of the fecal virome indicates high diversity in pigs infected by porcine endemic diarrhea virus in the United States. Virol J 15:95	Chen	2018
PMID 28074712	2017. High-throughput whole genome sequencing of porcine reproductive and respiratory syndrome virus from cell culture materials and clinical specimens using next-generation sequencing technology	Zhang	2017
PMID 19451168	2009. Fast and accurate short read alignment with Burrows-Wheeler transform	Li	2009
PMID 19505943	2009	Li	2079
PMID 19251739	2009. ABySS: a parallel assembler for short read sequence data. Genome Res 19:1117–1123	Simpson	2009
PMID 22506599	2012. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing	Bankevich	2012
PMID 27679478	2017. Influenza Research Database: an integrated bioinformatics resource for influenza virus research	Zhang	2017
PMID 23329690	2013. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol Biol Evol 30:772–780	Katoh	2013
PMID 19377059	2009. FastTree: computing large minimum evolution trees with profiles instead of a distance matrix. Mol Biol Evol 26:1641–1650	Price	2009
PMID 17996036	2007. BEAST: Bayesian evolutionary analysis by sampling trees. BMC Evol Biol 7:214	Drummond	2007
PMID 29942656	2018. Bayesian phylogenetic and phylodynamic data integration using BEAST 1.10	Suchard	2018
PMID 29722887	2018. MEGA X: molecular evolutionary genetics analysis across computing platforms. Mol Biol Evol 35:1547–1549	Kumar	2018
PMID 24264991	2013. Substitutions near the receptor binding site determine major antigenic change during influenza virus evolution	Koel	2013
PMID 29453058	2018. Antigenic and genetic evolution of contemporary swine H1 influenza viruses in the United States. Virology 518:45–54	Rajao	2018
PMID 24899438	2014. Hemagglutinin inhibition assay with swine sera. Methods Mol Biol 1161:295–301	Kitikoon	2014
-	2019	R Core Development Team. 2019. R: a lang	2019
-	2016. ggplot2: elegant graphics for data analysis. Springer-Verlag; New York, NY	Wickham H. 2016. ggplot2: elegant graphi	2016
PMID 22461226	A/H1N1 influenza virus	Gauger	2009
PMID 17719188	2008. Failure of protection and enhanced pneumonia with a US H1N2 swine influenza virus in pigs vaccinated with an inactivated classical swine H1N1 vaccine	Vincent	2007
PMID 16621020	2006. The immune response and maternal antibody interference to a heterologous H1N1 swine influenza virus infection following vaccination	Kitikoon	2006
PMID 30533826	2018. Complete genome sequences of two novel human-like H3N2 influenza A viruses, A/swine/Oklahoma/65980/2017 (H3N2) and A/Swine/Oklahoma/65260/2017 (H3N2), detected in swine in the United States. Microbiol Resour Announc 7:e01203-18	Zeller	2017

Evidence overview

Evidence 6

Types 6

Virus 4

Host 2

Evidence types

Genomic Evolution 1 Host Range Experiment 1 Molecular Adaptation 1 Recombination Or Reassortment 1 Spillover Event 1 Zoonotic Surveillance 1

Linked entities

Viruses

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Publication metadata

Journal: mSphere
Volume / Issue / Pages: 7 / 1 / e0080921
ISSN: 2379-5042
Journal country: United States
DOI: 10.1128/msphere.00809-21