Substitutions affecting the HA–NA– #receptor #balance preceded the emergence of the #pandemic 2009 #H1N1 virus

 

Abstract

Swine are a crucial species in influenza A virus (IAV) ecology, capable of supporting replication and consequently evolution of human, avian, and swine strains. They are also the source of the 2009 pandemic H1N1 virus (H1N1pdm09). Understanding how swine IAV breach the species barrier is essential for detection of potentially pandemic viruses, but is often overlooked compared to avian IAV. We hypothesize that the HA–NA balance of (pre)pandemic swine viruses is a key feature that needs adjustment as swine and humans differ in their sialoglycome. We focused on a set of (pre)pandemic swine viruses collected in Mexico following the H1N1pdm09 emergence. Phylogenetic analysis showed that the emergence was preceded by substitutions in HA and NA predicted to affect their function. Thus, HA acquired substitution A227E, previously shown to reduce receptor binding in H1N1pdm09, while NA obtained substitution S369N in the 2nd sialic acid binding site (2SBS) predicted to reduce NA cleavage. The substitutions’ effect on the HA–NA balance, was confirmed with biolayer interferometry using recombinant proteins attached to nanoparticles. Engineering recombinant attenuated influenza viruses with swine HA and NA with/without the mentioned substitutions, showed that the 2SBS substitution negatively affected replication in primary human and swine cultures. Interestingly, replication was restored by the HA substitution. Overall, we show that the emergence of H1N1pdm09 in humans was preceded by substitutions in HA and NA that were acquired in swine and adjusted the HA–NA balance. We hypothesize that adjustment of the HA–NA balance was a critical step for crossing the host–species barrier.

Source: 

Link: https://doi.org/10.1073/pnas.2609870123

____

Molecular #Epidemiology and #Evolution of Swine #Influenza A Viruses, #Vietnam, 2020–2024

 

Abstract

Swine influenza A viruses (IAV-S) caused the 2009 H1N1 pandemic and pose a future zoonotic and pandemic threat. Vietnam represents a critical hotspot for IAV-S emergence within East and Southeast Asia, with dense swine and human populations and intensive livestock trade. We conducted genomic surveillance of IAV-S in Vietnam during 2020–2024, extending previous surveillance from 2013–2019. We identified multiple co-circulating H1 and H3 clades, including pandemic H1N1, Eurasian avian-like, and European lineages, by conducting phylogenetic analysis of 56 IAV-S isolates (21 H1N1, 31 H1N2, and 4 H3N2). Three H1 clades persisted exclusively in Vietnam, circulating up to 12 years. Phylogeographic analysis revealed multiple independent introduction events from North America, Europe, China, Thailand, and Cambodia. We detected extensive reassortment that frequently involved pandemic H1N1 virus internal genes. We identified several lineage-specific mutations associated with mammalian adaptation. Our findings underscore the ongoing IAV-S evolution and need for sustained surveillance in Vietnam.

Source: 

Link: https://doi.org/10.3201/eid3210.260593

____

#Livestock production intensity and mucosal #IgA and #IgG responses to #H5N1 highly pathogenic avian #influenza A virus, North Carolina, 2021-2022

 

Abstract

Background. 

Direct livestock exposure is a risk factor for zoonotic influenza, including H5N1 highly pathogenic avian influenza (HPAI) A virus. But whether living in regions of high poultry and swine production intensity (PPI, SPI) increases risk of exposure to zoonotic influenza viruses independent of occupational livestock contact remains unclear. 

Objectives. 

To determine whether livestock workers and community members with no occupational livestock exposure in North Carolina, where poultry and swine production are increasingly co-located, are at higher risk of exposure to zoonotic influenza. 

Methods. 

Saliva samples from industrial livestock operation worker (ILO-W), ILO neighbor (ILO-N) and metropolitan area (Metro) households were analyzed for mucosal influenza A (H5N1, H1N1, and H3N2) hemagglutinin (HA) IgA and IgG antibodies to determine associations of PPI, SPI, exposure group, and detection of a swine-specific fecal contamination marker (Pig-2-Bac DNA) with influenza A antibody levels. 

Results. 

Residing in the highest PPI and SPI tertile was associated with significantly higher mucosal H5 and H1 HA IgA levels, including among residents without occupational livestock exposure. Households with occupational poultry or swine contact had significantly higher H5 IgA and IgG and H1 IgA levels compared to Metro households. In regression models accounting for clustering at the participant level, log10 anti-H5 HA mucosal IgA increased 0.16 (95% CI: 0.06, 0.27, p<0.005) and 0.10 (95% CI: 0.03, 0.17, p<0.005), per log10 increase in PPI and SPI, respectively, and 0.16 (95% CI: 0.03, 0.19, p<0.02) when Pig-2-Bac DNA was detected on household surfaces. 

Conclusions. 

Mucosal H5 HA IgA and IgG and H1 HA IgA were consistently elevated across different metrics of livestock exposure intensity, including residential exposure, occupational contact within a household, and a molecular marker of household swine fecal contamination in a state with intensive poultry and swine production.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.medrxiv.org/content/10.64898/2026.08.06.26359901v1

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#Bovine-derived #H5N1 #influenza virus efficiently infects lactating #swine via the #mammary gland

 

Abstract

Since 2024, highly pathogenic influenza A(H5N1) viruses have spread extensively among U.S. dairy cattle, where they replicate efficiently in the mammary gland and are shed at high titers in milk. To directly assess susceptibility of commercial swine populations to bovine-derived H5N1 virus, lactating sows with prior influenza virus vaccination histories representative of U.S. commercial swine production systems were inoculated via the intramammary route and co-housed with their 1-week-old piglets to evaluate disease outcomes, viral replication, and potential for vertical transmission. Intramammary inoculation of lactating sows resulted in sustained viral RNA shedding in milk, while piglets exhibited sporadic oral viral RNA positivity that mirrored viral kinetics in milk. Lesions in mammary tissue and viral antigen staining, as well as development of neutralizing antibody responses and changes in milk color and consistency, further confirmed infection in the sows. Despite these molecular findings, none of the animals developed overt clinical disease, and respiratory involvement was not noted during the study period. Collectively, we demonstrate that intramammary exposure results in productive influenza A(H5N1) virus infection in lactating sows despite their vaccination histories, indicating the potential threat of viral spillover into commercial swine populations. The clinically inapparent nature of infection presents a risk of subclinical spread and underscores the importance of expanding viral surveillance to swine.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Swine Health Information Center, 25-020

United States Department of Agriculture (USDA) National Institute of Food and Agriculture (NIFA), 2025-39601-44639

National Institutes of Health, P30 CA016058

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.07.18.739312v1

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Occupationally Exposed and General #Population #Antibody #Profiles to #Influenza A Viruses Circulating in #Swine as Indication of Zoonotic #Risk

 

Abstract

Persons with occupational exposure to swine might be at disproportionate risk for zoonotic swine influenza A virus. To evaluate human antibody responses, we tested serum or plasma from swine veterinarian, farm employee, and general population cohorts by hemagglutination inhibition assays against representative swine and human seasonal influenza vaccine strains. We analyzed hemagglutination inhibition data by antigenic cartography to assess strain relationships and reproduction number modeling to evaluate pandemic potential using age-stratified immunity profiles. Occupationally exposed groups had lower human seasonal vaccine uptake (45.5% vs. 70%) and lower odds of seropositivity to several H1 and H3 strains from swine than did general population cohorts. One swine strain exhibited significant antigenic drift (3.62 antigenic units) from its nearest vaccine strain. Multiple strains required lower reproduction number thresholds for pandemic spread (1.09–1.35) than recorded pandemic strains (1.46–1.80), demonstrating that population immunity gaps heighten zoonotic risk to circulating swine H1 and H3 strains.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/8/25-1995_article

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

 

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.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/8/25-1765_article

____

#Genetic and biological characterization of a #reassortant #H3N2 swine #influenza virus isolated in #China with internal genes from the 2009 pandemic #H1N1

 

Abstract

Swine influenza virus (SIV) not only causes significant losses to the pig industry but also poses a potential threat to human health due to its ability for cross-species transmission and zoonotic characteristics. In this study, 600 nasal swab samples were collected from pigs in Shandong Province and tested for SIV using RT-qPCR. One sample tested positive, and the virus was successfully isolated in 10-day-old specific-pathogen-free (SPF) embryonated chicken eggs. Subtype-specific RT-PCR and sequencing identified the isolate as H3N2, designated A/swine/Shandong/116/2022 (H3N2). Whole-genome sequencing and similarity analysis showed that PB2, PB1, PA, NP, and M genes were most similar to H1N1 viruses (97.71–99.67%), while HA, NA, and NS genes were closest to H3N2 viruses (96.06–97.85%), suggesting this isolate is a reassortant between H1N1 and H3N2 viruses. Phylogenetic analysis indicated that PB2, PB1, PA, NP, and M genes belong to the 2009 pandemic H1N1 (pdm/09 H1N1) lineage, HA and NA genes belong to the human-like H3N2 (HL H3N2) lineage, and the NS gene belongs to the triple-reassortant (TR) H1N2 lineage. Key amino acid analysis showed a monobasic HA cleavage site (PEKQTR/G), consistent with low pathogenicity, and residues 190V, 226I, and 228S, which may affect receptor binding. PB2 residues 271A, 590S, and 591R may influence viral replication and host adaptation. Compared with the human influenza vaccine strain A/Darwin/9/2021 (H3N2), several amino acid changes were found in HA antigenic sites A, B, C, and E, suggesting possible antigenic drift. In addition, clear differences were found in N-linked glycosylation sites between the isolate and vaccine strain, including loss of several glycosylation sites and the appearance of a new site at position 499, which may change virus antigenicity and immune recognition. Functional studies demonstrated that the isolate efficiently infected MDCK cells and replicated in the respiratory tissues of BALB/c mice, causing mild to moderate lung lesions without mortality or significant weight loss. In summary, the isolated is a multi-source reassortant virus with low pathogenicity, providing valuable insights into the genetic characteristics and epidemiology of H3N2 SIV circulating in pigs in China.

Source: 

Link: https://link.springer.com/article/10.1186/s12866-026-05324-w

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Breeding #pig #transport drives the dispersal of #swine #influenza A virus across #Europe

 

Abstract

Pigs serve as reservoirs of former human influenza A virus (IAV) H1N1 and H3N2 lineages and act as mixing vessels for diverse strains, facilitating the emergence of novel IAVs. Understanding the spread and evolution of swine IAVs (swIAVs) is therefore crucial to assess the risk of strains with zoonotic potential emerging. This study uses a phylogeographic framework to investigate the predictors of swIAV dispersal across Europe. All publicly available swIAV genomic sequences were retrieved and subsampled for the ten largest European pig-producing countries. Discrete phylogeographic reconstructions were conducted for H1, H3, N1, N2 encoding genes and all internal gene segments. Our analyses indicate that viral dispersal predominantly occurred from north-western to southern and eastern Europe, with frequent long-distance transitions between non-adjacent countries. We also extended the discrete phylogeographical analyses with generalized linear models to test the association between viral movement and potential predictors, such as live pig trade, pork trade, pig densities, farm sizes, or the geographic distance between key pig production zones. We find that breeding pig trade is the only consistently well-supported predictor of between-country transition events, whereas pork trade and geographic distance were not supported. This highlights that farms importing breeding pigs from multiple countries could act as hotspots for reassortment of diverse swIAV strains. Strengthening external biosecurity on farms with emphasis on quarantining breeding pigs, limiting long-distance transport, and implementing a One Health surveillance system for earlier detection of emerging strains, could help curb the rapid spread and evolution of swIAV in Europe.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.06.01.729471v1

____

#Zoonotic #infections and genomic #evolution associated with novel #reassortants swine-origin #influenza A viruses in #Spain

 

Abstract

Influenza A virus (IAV) circulates widely in European pig populations and continues to diversify through frequent introductions from humans, followed by reassortment within swine. Spain represents a particularly dynamic ecological setting due to the coexistence of intensive white pig production, extensive Iberian pig systems, and abundant wild boar populations. This study provides an integrated analysis of IAV evolution and genomic diversity in swine in Spain between 2019 and 2022, expanding on previous surveillance from 2016 to 2019. Sampling across 24 provinces yielded 66 new whole genome sequences from Iberian and white pigs. We identified 18 genotypes, including 11 novel reassortants not detected in our previous survey. Several genotypes, such as H1huN2 G21 and G22, H3N2 G23, and the unusual H3N1 G12, were exclusive to the country. Some genotypes were detected across white pigs, Iberian pigs, and wild boar in Toledo and Badajoz, suggesting viral flow among swine populations. Phylogenetic analyses revealed ongoing introductions of H1N1pdm09 from humans into pigs, generating at least five reassortant genotypes (G10, G16 to G19). These lineages incorporated pandemic internal cassettes and, in some cases, human seasonal N2 segments, highlighting the continued role of humans as a source of viral incursions. Conversely, four zoonotic infections (H1N1v) detected in Spain between 2022 and 2026 were linked to genotypes circulating in white pigs, underscoring the bidirectional nature of IAV transmission at the human swine interface. Overall, this study demonstrates that Spain provides ecological conditions conducive to IAV diversification, reassortment, and zoonotic risk. The findings reinforce the need for sustained One Health surveillance.

Competing Interest Statement

The A.G.-S. laboratory has received research support from Avimex, Dynavax, Pharmamar, and Accurius, outside of the reported work within the last three years. A.G.-S. has consulting agreements for the following companies involving cash and/or stock within the last three years: Castlevax, Amovir, Vivaldi Biosciences, Contrafect, Avimex, Pagoda, Accurius, Applied Biological Laboratories, Pharmamar, CureLab Oncology, CureLab Veterinary, Virofend and Prosetta, outside of the reported work. A.G.-S. has been an invited speaker in meeting events within the last three years organized by Seqirus, Novavax and Hipra. A.G.-S. is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York, outside of the reported work. The rest of the authors report no conflicts of interest.

Funder Information Declared

Centre for Research on Influenza Pathogenesis and Transmission (CRIPT), one of the National Institute of Allergy and Infectious Diseases (NIAID) funded Centres of Excellence for Influenza Research and Response (CEIRR), contract #75N93021C00014

Intramural Research Program of the National Library of Medicine at the US National Institutes of Health

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.05.22.724525v1

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Concurrent #Detection of #Swine-Origin #Influenza #H1N1 Virus in #Pigs and #Farmer, #Switzerland

 

Abstract

We report zoonotic transmission of Eurasian avian-like swine influenza A(H1N1) virus from pigs to a farmer. The pigs and farmer experienced influenza-like illness. Whole-genome sequencing revealed >99.9% isolate sequence identity between hosts. Our findings highlight the risk posed by enzootic swine influenza A virus and the need for genomic and epidemiologic surveillance.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/6/25-1487_article

____

G4 #Eurasian avian-like #H1N1 swine #influenza viruses exhibit enhanced #pathogenicity potential in mice and #pigs

 

Abstract

Currently circulating swine influenza viruses (SIVs) mainly include H1N1, H1N2, and H3N2 subtypes. In this study, two G4 genotype Eurasian avian-like (EA) H1N1 SIVs were isolated from 556 samples collected between 2023 and 2026. A systematic analysis was conducted on the two EA H1N1 isolates (FYD30 and YZF69) to assess their pandemic potential. The hemagglutinin (HA) proteins of both H1N1 viruses possessed residues 225E and 228S, indicating enhanced affinity for human-like alpha-2,6-linked sialic acid receptors, which was confirmed by receptor-binding assays. Polymerase activity tests demonstrated that the two SIVs exhibited significantly higher activity in mammalian cells, relative to avian cells, which is consistent with the efficient replication in mammalian cells. Challenge experiments revealed that both H1N1 caused significant pathogenicity in mice and pigs, with YZF69 exhibited higher virulence than FYD30. The higher virulence of YZF69 may be attributed to its molecular features, including the NP Q357K mutation, and an additional glycosylation site in HA. In conclusion, currently circulating EA H1N1 SIVs have acquired key molecular signatures of mammalian adaptation, exhibit enhanced virulence in mammals, and continue to undergo extensive reassortment driven by international swine trade. These findings highlight the potential pandemic risk of SIVs and underscore the urgent need for strengthened surveillance.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.05.12.724537v1

____

#Genetic and #biological characterization of #H9N2 avian #influenza viruses isolated from #swine in #China

 

Abstract

Background

H9N2 avian influenza virus (AIV) has been circulating in poultry in China for decades and are undergoing adaptation to mammals, posing potential pandemic risks. To investigate the prevalence of H9N2 AIVs in swine, we conducted surveillance in Shandong Province from 2021 to 2023.

Results

Two H9N2 influenza virus strains, A/swine/Shandong/417/2021(Sw/SD/417/21) and A/swine/Shandong/662/2022 (Sw/SD/662/22), were successfully isolated from swine and genetically characterized. Phylogenetic analyses showed that both isolates were reassortants containing gene segments from multiple H9N2 AIV lineages and closely related to currently circulating H9N2 AIV. Key molecular marker analysis revealed that both isolates carried mammalian-adaptive residues in the HA receptor-binding sites (183 N, 190 V, 226 L), a novel HA cleavage site variant (PSKSSRGL), PB2 mutations (A588V, E627V), and the M2 S31N substitution, suggesting potential adaptation to mammalian hosts and resistance to adamantane antivirals. Mice infection experiments demonstrated efficient viral replication in the respiratory tract, particularly in the lungs, but only mild histopathological changes were observed, with no significant weight loss or mortality, indicating low pathogenicity in mice. Serological surveillance of 3,172 swine serum samples showed a low prevalence of H9N2 influenza virus infection (0.44%), with positive samples sporadically distributed across regions and years.

Conclusion

In summary, although H9N2 AIV infection in swine is rare and generally mild, the presence of mammalian-adaptive markers and reassortant genomes highlights the potential risk of cross-species transmission and subclinical adaptation. Continuous avian–swine–human influenza surveillance is therefore essential to mitigate the potential threat posed by H9N2 AIV.

Source: 

Link: https://link.springer.com/article/10.1186/s12917-026-05501-z

____

Longitudinal #serum #proteomics analyses reveal #biomarkers for porcine #influenza and #coronavirus infections

 

Abstract

Respiratory virus infections affect both humans and livestock, causing considerable mortality and morbidity. While respiratory pathogens such as swine influenza A virus (pH1N1) and porcine respiratory coronavirus (PRCV) often present with overlapping clinical symptoms, their pathological trajectories and outcomes differ. Given the propensity for pathogen spillover and the use of pigs as a physiologically relevant large-animal translational model, we aimed to characterise host serum protein signatures that detect and differentiate pH1N1 from PRCV, enabling improved disease monitoring and control. Using high-resolution mass spectrometry-based proteomics, we identified 162 serum proteins that were significantly dysregulated across 3 infection timepoints (1, 5, and 12 days post-infection (DPI)), with signatures correlating with viral shedding and lung pathology as early as 1 DPI. Notably, multiplexed targeted analysis of a subset of proteins in an independent cohort from a different breed and geographic location demonstrated detection, femtomole-level targeted quantitation, and validation of SRGN as a diagnostic marker for pH1N1 and PRCV (AUC=0.85). Further, SOD1 was validated as an early marker for PRCV, increasing as early as 1 DPI (AUC= 0.9). Finally, a multi-peptide signature composed of SRGN, SOD1, and RAN demonstrated reasonable predictive power for pH1N1 (AUC=0.75) and PRCV (AUC=0.65) at 1 DPI. Our data validate the proteomic screening, provide insights into the role of early protein markers in distinguishing respiratory viral infections, and pave the way for the development of point-of-care diagnostics and targeted prevention strategies, enhancing preparedness against emerging zoonotic threats.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

UKRI Biotechnology and Biological Sciences Research Council (BBSRC), BB/X019780/1, BBS/E/PI/230002A, BBS/E/PI/230002B, BBS/E/PI/230002C, BS/E/PI/23NB0004

University of Surrey, https://ror.org/00ks66431

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.04.21.719833v1

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ONWARD: a #OneHealth, pan - #European multidisciplinary #network advancing #surveillance, #research, clinical management and control of zoonotic #hepeviruses

 

Highlight

• HEV remains the leading cause of acute viral hepatitis in Europe

• Surveillance and diagnostics for HEV are heterogeneous across EU/EEA

• Zoonotic HEV circulates widely in pigs, wildlife and food chains

• Rat HEV expands the zoonotic spectrum and clinical burden in Europe

• ONWARD integrates One Health surveillance, research and capacity building

Abstract

Zoonotic hepeviruses, particularly hepatitis E virus (HEV, species Paslahepevirus balayani) represent a major yet underestimated public health challenge in Europe. Despite being the leading cause of acute viral hepatitis, surveillance, diagnostic practices and prevention strategies remain heterogeneous across EU/EEA countries, limiting comparability and hindering accurate burden estimates. Underdiagnosis is further compounded by extrahepatic manifestations and the growing impact of chronic HEV infection in immunocompromised patients. At the human–animal–environment interface, zoonotic HEV circulates widely in domestic pigs, wildlife and food products, while coordinated surveillance and control measures remain inconsistently implemented. The recent recognition of ratHEV (species Rocahepevirus ratti) as a cause of acute and chronic hepatitis in Europe further expands the spectrum of zoonotic hepevirus infections and underscores the need for integrated One Health approaches. To address these challenges, the One Health Zoonotic Hepevirus Network (ONWARD; COST Action CA24140) was launched in 2025 as a pan-European, multidisciplinary collaboration uniting experts across human, veterinary, food safety and environmental health sectors. ONWARD aims to harmonise diagnostic tools, strengthen clinical research, integrate multisectoral surveillance, promote capacity building and support evidence-based policy development. By fostering coordination with European stakeholders ONWARD provides a structured framework to strengthen preparedness, surveillance and response to zoonotic hepevirus threats across Europe.

Source: 

Link: https://www.sciencedirect.com/science/article/pii/S1386653226000338?dgcid=rss_sd_all

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Genetic characterization of a novel triple - #reassortant #influenza #H1N2 virus from #pigs, #China, 2021

 

Abstract

Swine influenza virus (SIV) is a highly contagious respiratory pathogen in pigs, with bidirectional transmission posing a potential threat to human health. In this study, nasal swab samples were collected from pigs in Shandong Province, China, and yielded an H1N2 SIV strain, designated A/swine/Shandong/QD726/2021 (H1N2). Whole-genome sequencing was performed for Sw/SD/QD726/2021, and phylogenetic analysis was conducted together with 156 Chinese H1N2 reference sequences obtained from the Global Initiative on Sharing All Influenza Data (GISAID) database and the National Center for Biotechnology Information (NCBI) Influenza Virus Resource database. The results indicated that Sw/QD726/2021 represents a novel reassortant genotype (G21), with the HA gene derived from Eurasian avian-like H1N1 (EA H1N1), the NA and NS genes from triple-reassortant H1N2 (TR H1N2), and the remaining internal genes (PB2, PB1, PA, NP, M) from the 2009 pandemic H1N1 (pdm/09 H1N1). Key amino acid analysis revealed N31 in M2, responsible for adamantane resistance, and S42 in NS1, which influences viral virulence in mouse models. BALB/c mouse experiments demonstrated efficient viral replication in the lungs and nasal turbinates, accompanied by moderate body weight loss and lung lesions, indicating only moderate pathogenicity. These findings underscore the ongoing evolution of H1N2 SIV in pigs and emphasize the importance of enhanced surveillance and preventive strategies to mitigate public health risks.

Source: 

Link: https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2026.1779293/full

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‘Our problem here is the #pig #Ebola’: local accounts of #epizootics preceding Ebola #outbreaks in north-eastern #DRC

 

Abstract

Introduction 

Despite their potential relevance for outbreak understanding, epizootic reports associated with Ebola scarcely appear in biomedical literature. This study examines local accounts of animal deaths preceding the 2012 and the 2017 Ebola outbreaks in the north-eastern Democratic Republic of the Congo (DRC).

Methods 

The analysis is based on retrospective interviews conducted with scientists deployed during these two Ebola outbreaks, as well as testimonies collected in 2022 and 2023 from local residents, clinicians and veterinarians. It also draws on local archives to examine how reports of animal deaths were framed and understood in light of a new epidemic situation.

Results 

Selective pressures that favour certain wild animal species, along with social practices such as bushmeat hunting, contribute to a narrowing of focus during outbreak investigations. This has contributed to overlooking some testimonies from marginalised local actors, which remain unpublished to this day. Animal death reports, however, need to be read in their social context. During the 2017 Ebola outbreak, local breeders framed their concerns about pig mortality into a question to be addressed by global health researchers—even though the deaths were not linked to Ebola but were likely caused by an unrelated pathogen, the African swine fever virus.

Conclusion 

Beyond their biological relevance, epizootics can offer insight into the social contexts in which epidemics are identified. These epizootics can shed light on local experiences of diseases, illustrating local priorities and sense-making processes.

Data availability statement

Data sharing is not applicable as no data sets were generated and/or analysed for this study.

DOI: https://doi.org/10.1136/medhum-2025-013586

Footnotes

Contributors: JV conceptualised the study, conducted the research and wrote the manuscript. JV is the guarantor.

Funding: The author received support from Sciences Po Medialab and IFAS (Institut Français d'Afrique du Sud) for fieldwork in the DRC in 2022 and 2023.

Competing interests: None declared.

Patient and public involvement: Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.

Provenance and peer review: Not commissioned; externally peer reviewed.

Source: 

Link: https://mh.bmj.com/content/early/2026/04/01/medhum-2025-013586

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Porcine #influenza #mAbs to #H3, #H5, and #H7 hemagglutinins recognize H3 egg adapted site and target the HA stem

 

Abstract

Introduction

Monoclonal antibodies (mAbs) are critical tools for elucidating viral evolution, informing vaccine design, and developing antiviral therapeutics. Large-animal models, such as the pig, that closely mirror human immune responses are essential for understanding influenza immunity.

Methods

Pigs were either infected or sequentially immunized with influenza viruses and monoclonal antibodies directed against H3, H5, and H7 influenza virus haemagglutinins were isolated. Antibody specificity, breadth, epitope targeting (head versus stem), neutralizing capacity, and Fc-mediated activity were assessed across influenza subtypes.

Results

Pigs generated both strain-specific and broadly reactive mAbs targeting haemagglutinin head and stem epitopes. An H3-specific mAb (H3–57) selectively recognized the egg-adapted L194P mutation associated with reduced human vaccine effectiveness. H5 and H7 immunization induced neutralizing antibodies, including cross-group stem mAbs reactive with H1, H3, and H5 haemagglutinins. Fc-mediated activity correlated with antibody binding strength rather than epitope location.

Conclusions

These findings demonstrate that pigs mount antibody responses closely resembling those observed in humans, including recognition of conserved stem epitopes and adaptive head mutations. Porcine mAbs represent powerful new tools for dissecting influenza immunity, guiding vaccine design, and enhancing pandemic preparedness using a physiologically relevant large-animal model.

Source: 

Link: https://academic.oup.com/discovimmunology/article/5/1/kyag006/8503709

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Impact of an #aminoacid #deletion detected in the #hemagglutinin (HA) #antigenic site of swine #influenza A virus field strains on HA antigenicity

 

ABSTRACT

Swine influenza A virus (swIAV) is an important pathogen with regard to both the swine industry and public health. The pandemic A(H1N1) 2009 outbreak was caused by the swine-origin pandemic A(H1N1) 2009 [A(H1N1)pdm09] virus. Several reports have shown that several amino acid substitutions in the hemagglutinin (HA) antigenic sites can alter HA antigenicity. However, the impact of the amino acid deletion at position 155 on HA antigenicity remains unknown. In this study, we have isolated 11 samples of swIAVs from seven pig farms in Japan and found an amino acid deletion at position 155 of the HA region in one of the isolates of the H1N2 subtype. To examine the impact of this amino acid deletion on viral replication and HA antigenicity, we generated recombinant influenza A viruses possessing the H1 HA gene encoding either an artificial insertion or deletion of glycine at position 155. The growth kinetics of these recombinant viruses in two different cell lines demonstrated that the effect of amino acid deletion at position 155 of H1 HA on viral replication is limited. In contrast, microneutralization assay-based neutralization titers revealed that amino acid deletion significantly altered HA antigenicity. These results demonstrate that a naturally occurring amino acid deletion at position 155 in an H1 HA antigenic site can markedly alter HA antigenicity with only a limited impact on replication in vitro, highlighting the need to monitor such variants in swine populations and to assess their zoonotic potential.

Source: 

Link: https://journals.asm.org/doi/full/10.1128/jvi.01820-25?af=R

____

Characterization of a reassortant #H3N2 swine #influenza virus with 2009 pandemic internal #genes and enhanced potential for zoonotic #risk

 

Highlights

• A swine influenza virus H3N2 subtype was isolated during epidemiological survey.

• It is a complex and novel reassortant, and acquired accumulation of adaptive mutations.

• Both rescue and parent strains demonstrated efficient replication in mammalian cells.

• Key residues of the H3N2 HA collectively enhance the binding preference for human-type receptor.

• The rescued H3N2 cause significant pulmonary pathological damage in mice.

Abstract

Pigs serve as key "mixing vessels" for influenza A viruses, playing a critical role in cross-species transmission, while the H3N2 subtype represents an important lineage within the swine influenza virus (SIV) family. In this study, a novel reassortant H3N2 SIV strain, designated A/Swine/Jiangsu/YZ07/2024, was isolated from pigs exhibiting clinical symptoms in Northern Jiangsu, China during epidemiological survey. Genetic analysis revealed that the virus is a complex reassortant, with the internal genes (M, NP, PB1, PB2, PA) originated from the 2009 pandemic H1N1 lineage, the NS gene exhibiting a North American triple reassortant origin (human-avian-swine origin), and the HA and NA genes belonging to the human-like lineage. Although neither the rescued virus nor its parental strain could replicate effectively in chicken embryos and chicken cells, both demonstrated efficient replication in mammalian cells, reflected by the much higher polymerase activity in mammalian versus chicken cells. The key residues of HA protein (190D, 225D and 228S) collectively enhanced the binding preference for human-type α-2,6-linked sialic acid receptors, which was confirmed by receptor binding assays. Furthermore, mouse infection experiments using the rescued H3N2 demonstrated efficient viral replication in nasal turbinates and lung tissues, accompanied by significant pulmonary pathological damage. These findings indicate that the YZ07 strain, through the vast reassortment and accumulation of adaptive mutations, has acquired potential zoonotic risk, underscoring the importance of surveillance of swine influenza viruses.

Source: 

Link: https://www.sciencedirect.com/science/article/abs/pii/S0378113526000684?via%3Dihub

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Genetic Characterization and Evolutionary #Insights of Novel #H1N1 Swine #Influenza Viruses Identified from #Pigs in #Shandong Province, #China

 

Abstract

Influenza A viruses exhibit broad host tropism, infecting multiple species including humans, avian species, and swine. Swine influenza virus (SIV), while primarily circulating in porcine populations, demonstrates zoonotic potential with sporadic human infections. In this investigation, we identified two H1N1 subtype swine influenza A virus strains designated A/swine/China/SD6591/2019(H1N1) (abbreviated SD6591) and A/swine/China/SD6592/2019(H1N1) (abbreviated SD6592) in Shandong Province, China. The GenBank accession numbers of the SD6591 viral gene segments are PV464931-PV464938, and the GenBank accession numbers corresponding to each of the eight SD6592 viral gene segments are PV464939-PV464946. Phylogenetic and recombination analyses suggest potential evolutionary differences between the isolates. SD6591 displayed a unique triple-reassortant genotype: comparative nucleotide homology assessments demonstrated that the PB2, PB1, NP, NA, HA, and NEP genes shared the highest similarity with classical swine-origin H1N1 viruses. In contrast, SD6592 maintained genomic conservation with previously characterized H1N1 swine strains, although neither of these two isolates exhibited significant intrasegmental recombination events. Through comprehensive sequence analysis of these H1N1 SIVs, this study provides preliminary insights into their evolutionary history and underscores the persistent risk of cross-species transmission at the human–swine interface. These findings establish an essential foundation for enhancing national SIV surveillance programs and informing evidence-based prevention strategies against emerging influenza threats.

Source: 

Link: https://www.mdpi.com/1999-4915/18/1/117

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