Pigs are highly susceptible to but do not transmit mink-derived highly pathogenic avian influenza virus H5N1 clade 2.3.4.4b.

Taeyong Kwon¹ Jessie D Trujillo¹ Mariano Carossino² Eu Lim Lyoo¹ Chester D McDowell¹ Konner Cool¹ Franco S Matias-Ferreyra¹ Trushar Jeevan³ Igor Morozov¹ Natasha N Gaudreault¹ Udeni B R Balasuriya² Richard J Webby³ Nikolaus Osterrieder¹ Juergen A Richt¹

Affiliations 3 institutions

Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA.
Louisiana Animal Disease Diagnostic Laboratory and Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, USA.

PMID38712345 DOI10.1080/22221751.2024.2353292 Year2024 Journal Emerging microbes & infections Emerg Microbes Infect Languageeng Statusppublish

Abstract

ABSTRACTRapid evolution of highly pathogenic avian influenza viruses (HPAIVs) is driven by antigenic drift but also by reassortment, which might result in robust replication in and transmission to mammals. Recently, spillover of clade 2.3.4.4b HPAIV to mammals including humans, and their transmission between mammalian species has been reported. This study aimed to evaluate the pathogenicity and transmissibility of a mink-derived clade 2.3.4.4b H5N1 HPAIV isolate from Spain in pigs. Experimental infection caused interstitial pneumonia with necrotizing bronchiolitis with high titers of virus present in the lower respiratory tract and 100% seroconversion. Infected pigs shed limited amount of virus, and importantly, there was no transmission to contact pigs. Notably, critical mammalian-like adaptations such as PB2-E627 K and HA-Q222L emerged at low frequencies in principal-infected pigs. It is concluded that pigs are highly susceptible to infection with the mink-derived clade 2.3.4.4b H5N1 HPAIV and provide a favorable environment for HPAIV to acquire mammalian-like adaptations.

Supporting text Virus Host Location

clade 2.3.4.4b 19 H5N1 82 highly pathogenic avian influenza virus 13 mammalian-like adaptations, mink isolate, transmission 1 Pigs 12 Influenza A Virus, H5N1 Subtype 300 Mink 48 Orthomyxoviridae Infections 228 Swine Diseases 153 Animals 1948 Spain 25 Swine 258 Viral Proteins 152 Virus Shedding 51

Evidence records

3 total

Experimental Infection

2 records · 2 evidence types

Evidence type Pathogenicity Experiment

1 records

OVE8031 Pathogenicity Experiment

Key finding

Experimental infection of pigs with a mink-derived clade 2.3.4.4b H5N1 HPAIV from Spain caused interstitial pneumonia and necrotizing bronchiolitis with high viral titers in the lower respiratory tract.

Virus

Host

Location

Supporting text

This study aimed to evaluate the pathogenicity and transmissibility of a mink-derived clade 2.3.4.4b H5N1 HPAIV isolate from Spain in pigs. Experimental infection caused interstitial pneumonia with necrotizing bronchiolitis with high titers of virus present in the lower respiratory tract and 100% seroconversion.

Method: experimental infection | pathological examination of lungs | viral titration or viral load analysis
Experimental system: experimental infection in pigs

Evidence type Host Range Experiment

1 records

OVE8035 Host Range Experiment

Key finding

Pigs were experimentally infected and shown to be highly susceptible to the mink-derived clade 2.3.4.4b H5N1 highly pathogenic avian influenza virus.

Virus

Host

Location

Supporting text

It is concluded that pigs are highly susceptible to infection with the mink-derived clade 2.3.4.4b H5N1 HPAIV.

Method: experimental infection | virus titration | serological analysis | pathology assessment
Sample type: lower respiratory tract
Experimental system: animal infection model (pig challenge experiment)

Functional Mechanism

1 records · 1 evidence types

Evidence type Molecular Adaptation

1 records

OVE8034 Molecular Adaptation

Key finding

PB2-E627K and HA-Q222L mutations, associated with mammalian adaptation, emerged at low frequencies in pigs infected with the mink-derived clade 2.3.4.4b H5N1 HPAIV isolate from Spain.

Virus

Host

Location

Supporting text

Notably, critical mammalian-like adaptations such as PB2-E627 K and HA-Q222L emerged at low frequencies in principal-infected pigs. It is concluded that pigs are highly susceptible to infection with the mink-derived clade 2.3.4.4b H5N1 HPAIV and provide a favorable environment for HPAIV to acquire mammalian-like adaptations.

Genes or proteins: PB2 | HA
Mutations: PB2-E627K | HA-Q222L
Mechanism types: host-range expansion | receptor binding

References

55 references

Reference network

Force-directed citation graph. OmniVira-indexed references are prioritized and recursively expanded up to three steps.

243 nodes · 295 links

Drag nodes to explore citation neighborhoods


PMID 22371588	A distinct lineage of influenza A virus from bats	Tong	2012
PMID 24130481	New world bats harbor diverse influenza A viruses	Tong	2013
PMID 1566583	Hemagglutinin activation of pathogenic avian influenza viruses of serotype H7 requires the protease recognition motif R-X-K/R-R	Vey	1992
PMID 10484749	Genetic characterization of the pathogenic influenza A/Goose/Guangdong/1/96 (H5N1) virus: similarity of its hemagglutinin gene to those of H5N1 viruses from the 1997 outbreaks in Hong Kong	Xu	1999
PMID 18598616	Toward a unified nomenclature system for highly pathogenic avian influenza virus (H5N1)	WHO/OIE/FAO H5N1 Evolution Working Group	2008
-	Evolution of the influenza A(H5) haemagglutinin: WHO/OIE/FAO H5 Working Group reports a new clade designated 2	World Health Organization	2015
PMID 35726917	Has epizootic become enzootic? Evidence for a fundamental change in the infection dynamics of highly pathogenic avian influenza in Europe, 2021. mBio. 2022;13(4):e0060922	Pohlmann	2022
PMID 35302933	Intercontinental movement of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4 virus to the United States, 2021	Bevins	2022
PMID 16554799	Influenza virus receptors in the human airway	Shinya	2006
-	Avian influenza weekly update number	World Health Organization	2023
PMID 28243942	H5 influenza, a global update	Harfoot	2017
-	Assessment of risk associated with recent influenza A (H5N1) clade 2	World Health Organization	2022
PMID 36695488	Highly pathogenic avian influenza A(H5N1) virus infection in farmed minks, Spain, October 2022	Aguero	2023
PMID 21900171	2009 pandemic H1N1 influenza virus causes disease and upregulation of genes related to inflammatory and immune responses, cell death, and lipid metabolism in pigs	Ma	2011
-	A simple method of estimating fifty per cent endpoints12. Am J Epidemiol 1938;27(3):493–497	Reed	1938
PMID 33028154	SARS-CoV-2 infection, disease and transmission in domestic cats	Gaudreault	2020
PMID 20202440	Influenza A pandemic (H1N1) 2009 virus infection in domestic cat	Sponseller	2010
PMID 32170698	Serum virus neutralization assay for detection and quantitation of serum neutralizing antibodies to influenza A virus in swine	Gauger	2020
PMID 35936354	Evaluating alpha-galactosylceramide as an adjuvant for live attenuated influenza vaccines in pigs	Artiaga	2022
PMID 28008819	Effects of PB1-F2 on the pathogenicity of H1N1 swine influenza virus in mice and pigs	Lee	2017
PMID 32170681	Complete genome sequencing of influenza A viruses using next-generation sequencing	Lee	2020
PMID 22528160	Influenza A virus molecular virology techniques	Zhou	2012
PMID 11811679	Universal primer set for the full-length amplification of all influenza A viruses	Hoffmann	2001
PMID 27350259	Origins of the 2009 H1N1 influenza pandemic in swine in Mexico	Mena	2016
PMID 27426214	The ecology and adaptive evolution of influenza A interspecies transmission	Joseph	2017
PMID 18093945	Identification of H2N3 influenza A viruses from swine in the United States	Ma	2007
PMID 19465683	Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans	Garten	2009
-	Tool for influenza pandemic risk assessment (TIPRA)	World Health Organization	2020
PMID 25991697	Swine as a model for influenza A virus infection and immunity	Rajao	2015
PMID 9696833	Molecular basis for the generation in pigs of influenza A viruses with pandemic potential	Ito	1998
PMID 28688206	Absence of clinical disease and contact transmission of HPAI H5NX clade 2.3.4.4 from North America in experimentally infected pigs	Kaplan	2017
PMID 37347930	Low susceptibility of pigs against experimental infection with HPAI virus H5N1 clade 2.3.4.4b	Graaf	2023
PMID 37987580 In OmniVira	Highly Pathogenic Avian Influenza A(H5N1) Virus Clade 2.3.4.4b Infections in Wild Terrestrial Mammals, United States, 2022.	Elsmo	2023
PMID 36918379 In OmniVira	Highly Pathogenic Avian Influenza A(H5N1) Virus in a Harbor Porpoise, Sweden.	Thorsson	2023
PMID 36688676	Highly pathogenic avian influenza H5N1 virus infections in wild Red foxes ( Vulpes vulpes ) show neurotropism and adaptive virus mutations	Bordes	2023
PMID 26946338	Susceptibility of swine to H5 and H7 low pathogenic avian influenza viruses	Balzli	2016
PMID 12843064	Pathogenic and antigenic properties of phylogenetically distinct reassortant H3N2 swine influenza viruses cocirculating in the United States	Richt	2003
PMID 8077918	Potential for transmission of avian influenza viruses to pigs	Kida	1994
PMID 19919303	Efficient transmission of swine-adapted but not wholly avian influenza viruses among pigs and from pigs to ferrets	De Vleeschauwer	2009
PMID 9878612 In OmniVira	Characterization of avian H5N1 influenza viruses from poultry in Hong Kong.	Shortridge	1998
PMID 16051873	Studies of H5N1 influenza virus infection of pigs by using viruses isolated in Vietnam and Thailand in 2004	Choi	2005
PMID 37812908	Characterization of highly pathogenic clade 2.3.4.4b H5N1 mink influenza viruses	Maemura	2023
PMID 19359528	Isolation and genetic characterization of H5N2 influenza viruses from pigs in Korea	Lee	2009
PMID 20181719	PB2 residue 271 plays a key role in enhanced polymerase activity of influenza A viruses in mammalian host cells	Bussey	2010
PMID 19884910	H5N1 influenza viruses: outbreaks and biological properties	Neumann	2010
PMID 20016035	Role of host-specific amino acids in the pathogenicity of avian H5N1 influenza viruses in mice	Kim	2010
PMID 22723413 In OmniVira	Airborne transmission of influenza A/H5N1 virus between ferrets.	Herfst	2012
PMID 24725402	Identification, characterization, and natural selection of mutations driving airborne transmission of A/H5N1 virus	Linster	2014
PMID 11546875	Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses	Hatta	2001
PMID 19119420	Transmission of influenza virus in a mammalian host is increased by PB2 amino acids 627 K or 627E/701N	Steel	2009
PMID 26082035	Identification of mammalian-adapting mutations in the polymerase complex of an avian H5N1 influenza virus	Taft	2015
PMID 25409547	The K526R substitution in viral protein PB2 enhances the effects of E627 K on influenza virus replication	Song	2014
PMID 16543414 In OmniVira	Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus.	Stevens	2006
PMID 37535475	Highly pathogenic avian influenza A(H5N1) virus infection on multiple fur farms in the South and Central Ostrobothnia regions of Finland, 2023	Lindh	2023
PMID 37485254	Avian influenza overview April–June 2023	Adlhoch	2023