Thursday, July 16, 2026

EID Journal: Detection of Highly Pathogenic Avian Influenza A(H5N1) Clade 2.3.4.4b Genotype D1.2 Virus in Swine after Experimental Inoculation

 

#19,250

Although reports have been sporadic, over the past 2 decades we've seen growing field and laboratory evidence that H5N1 can infect pigs, albeit often asymptomatically. A few past reports include:






In May of 2023, in Netherlands: Zoonoses Experts Council (DB-Z) Risk Assessment & Warning of Swine As `Mixing Vessels' For Avian Flu, we looked at growing concerns in Europe that avian H5N1 could increase its pandemic threat by spreading (and evolving) in farmed swine.
But the reality is, testing for avian flu viruses in pigs is both voluntary and rare
Surveillance is generally passive, and since avian flu in pigs is usually mild, and self-limiting - and there could be significant downsides to reporting it (quarantines, economic losses, stigma, etc.) -  there is little incentive to delve deeper. 
According to the USDA, as of Sept.1, 2025 there were 74.5 million hogs and pigs on U.S. farms, and according to their last published Influenza A Virus in Swine Surveillance report (Q4), in they tested 977 samples in 2025.

The USDA further notes:

Due to the voluntary nature of this surveillance, the information in this report cannot be used to determine regional and/or national incidence, prevalence, or other epidemiological measures, but it may help identify IAV-S trends.
All of which suggests that were HPAI H5 to spillover into commercial swine - in the U.S. or elsewhere in the world - we'd be hard pressed to detect it.

All of which brings us to an EID research article, published yesterday, which finds (unlike previous studies on other H5 strains) that genotype D1.2 appears well suited to mildly or asymptomatically infect, and replicate systemically, in pigs. 

Due to its length, and technical nature, I've only posted the link, abstract, and some extended highlights.  But many will want to read it in its entirety.

I'll have a brief postscript after the break.

Research

Detection of Highly Pathogenic Avian Influenza A(H5N1) Clade 2.3.4.4b Genotype D1.2 Virus in Swine after Experimental Inoculation

Hannah Seger, Amy L. Baker, Alexandra C. Buckley, Tavis K. Anderson, Alexey Markin, Alessandra Campos, Bruno Caetano Trindade, Marissa Vincent, Giovana Ciacci Zanella, Mia Torchetti, Kristina Lantz, and Bailey Arruda

Abstract

Highly pathogenic avian influenza H5NX clade 2.3.4.4b viruses continue to circulate globally. Reintroduction of Eurasian lineage viruses into North America and reassortment with endemic low pathogenicity strains have resulted in new genotypes, including D1.2. To assess pathogenicity and cellular tropism, we intranasally inoculated genotype D1.2 virus into pigs.

We isolated virus from nasal secretions from most inoculated animals for multiple days. At 5 days postinoculation, PCR and immunohistochemistry detected virus in musculoskeletal, respiratory, digestive, lymphatic, and nervous systems and isolates from meat juice.

At 35 days postinoculation, we detected viral antigen and low levels of RNA in the brain of an animal with lesions consistent with a viral etiology and found viral antigen in the ethmoid of 2 animals.

Consistent detection in nasal swab specimens, combined with subclinical respiratory infection, systemic distribution, and protracted detection of clade 2.3.4.4b virus in swine, suggest identifying infection in commercial swine without overt respiratory signs could be difficult.

(SNIP)

On October 29, 2024, HPAI H5N1 clade 2.3.4.4b genotype D1.2 was confirmed in 1 sow housed in a backyard animal holding in Oregon, USA (15). We sought to assess the pathogenicity and cellular tropism of an HPAI H5N1 strain that was collected from that Oregon farm site in other swine by experimental infection via an intranasal route. The animal study (Appendix 1 Figure 1) was conducted in compliance with the Institutional Animal Care and Use Committee of the US Department of Agriculture Agricultural Research Service National Animal Disease Center under the Biosafety Level 3 guidelines.

        (SNIP)

Subclinical Respiratory and Mild Enteric Signs Observed

We compiled results for the clinical scoring system (Appendix 1 Table 1) into clinical scores (Appendix 1 Table 2). We did not observe respiratory clinical signs or fever in any animal throughout the study (Appendix 1 Tables 2, 3). We observed moderate diarrhea in 1 inoculated animal, starting at 3 DPI through necropsy at 5 DPI. We noted lethargy and diarrhea in the 3 remaining inoculated animals at 7 DPI, resolving at 14 DPI, and anorexia at 7 and 8 DPI. We did not note enteric signs in control animals.

        (SNIP)

We documented evidence of replication in multiple tissues and detection and viral isolation in nasal secretions of all intranasally (2 mL) inoculated pigs across multiple days. Other studies in swine have reported inconsistent detection in nasal swab specimens, limited detection outside the respiratory tract, and variable transmission (20,34; H. Feldmann et al., unpub. data, External Link).).

The consistent detection in nasal secretions, broader viral distribution within tissues, and protracted detection of low viral levels in 2 of 3 animals necropsied at 35 DPI documented in this work compared with the other studies might reflect study design, host, strain, or a combination of those. The more consistent detection in nasal secretions, turbinate and ethmoid compared with the trachea and lung within this study could suggest other viral mechanisms of host and tissue tropism beyond α-2,3 and α-2,6 sialic acid distribution that have not yet been characterized in swine (35).

(SNIP)

In conclusion, the intercontinental circulation of HPAI H5Nx viruses of the Gs/Gd lineage is a historic occurrence that has resulted in the infection of many avian and mammalian species with variable clinical manifestations, ranging from subclinical infections to mass mortality events. Host responses to HPAI infection, expression of clinical disease, and associated pathology vary depending on numerous interactions including the host, route of infection, dose, day postinfection, and virus strain (1). In this study, we observed no apparent respiratory or systemic signs and minimal neutralizing antibody response, despite consistent detection in nasal swab specimens and systemic distribution including skeletal muscle in inoculated animals.
Our data raise concerns over our ability to identify infection in commercial swine that do not exhibit overt respiratory signs while also exhibiting minimal neutralizing antibody response in affected animals. The apparent increased fitness of clade 2.3.4.4b H5Nx viruses and their reassortants in swine raises concerns over public health risks and highlights the need to clarify mammalian adaption and reassortment potential and supports the need for continued surveillance. 

Dr. Seger is an anatomical pathology resident at Iowa State University Veterinary Diagnostic Laboratory. Her research efforts focus on infectious disease pathology of food animal diseases of human importance.
 
Although this research is limited to HPAI H5N1 genotype D1.2, we continue to follow a great many other novel flu viruses - equally poorly tracked - spillover and/or spread in swine. 

 The CDC's IRAT (Influenza Risk Assessment Tool) lists 3 North American swine viruses as having at least some pandemic potential (2 added in 2019).
H1N2 variant [A/California/62/2018] Jul 2019  5.8 5.7 Moderate
H3N2 variant [A/Ohio/13/2017]         Jul 2019  6.6 5.8 Moderate
H3N2 variant [A/Indiana/08/2011]     Dec 2012 6.0 4.5 Moderate
There is even greater diversity among swine flu viruses around the globe, with China's EA H1N1 `G4' virus often cited as the world's biggest pandemic threat. We've also followed repeated spillovers in Brazil, and last year the Eurasian 1C Swine Influenza A Virus was labeled a `high pandemic risk'.

But our reluctance to aggressively test livestock (pigs, cattle, sheep, goats, mink, etc.) for novel viruses means that we are likely only seeing the tip of the viral iceberg. 

Which could end up being a mistake of titanic proportions.