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Quantifying the #zoonotic #risk profile of European #influenza A viruses in #swine from 2010 to 2020 inclusive

ABSTRACT H1 and H3 influenza A viruses (IAVs) circulating in European pigs are markedly distinct from those circulating in other global swine populations . These viruses exhibit significant genetic diversity , further expanded by periodic interspecies transmission of IAVs from humans into pigs , followed by sustained circulation. Several zoonotic IAV infections in humans in Europe have been associated with the 1C lineage of H1 IAVs . Given the predominance of H1 detections in pigs and their zoonotic potential, we quantified antigenic evolution of H1 viruses in European pigs using ferret and pig models and assessed diversity relative to swine IAV vaccine strains. Ferret and swine antisera comparisons revealed no significant differences in antibody responses . Viruses of the 1A.3.3.2 clade exhibited reduced cross-reactivity to human seasonal vaccine strains from 2009. Viruses of the 1B.1.2.2 clade showed no cross-reactivity to the 1978 human seasonal influenza viruses nor to candidate va...

A G219A #hemagglutinin #substitution increases #pathogenicity and viral #replication of Eurasian avian-like #H1N1 swine #influenza viruses

Abstract The Eurasian avian-like swine (EA) H1N1 virus has been widely prevalent in the Chinese swine population and has caused infections in human . However, knowledge regarding its pathogenic mechanisms remains limited. In this study, we analyzed the pathogenic determinants of two G4 genotype EA H1N1 viruses (A/Swine/Guangdong/SS12/2017 and A/Swine/Jiangxi/1110/2017) with differing pathogenicity by constructing a series of reassortant and mutant viruses . The HA-G219A mutation was found to be determinant of pathogenicity in mice. Subsequent analyses revealed that this mutation enhances viral replication in human cells , improves thermal stability , reduces HA activation pH, and alters receptor-binding properties . Furthermore, HA-G219A mutation may be an adaptive mutation that facilitates influenza virus adaptation to swine , with its prevalence increasing in the swine population. This mutation may support cross-species transmission of EA H1N1 swine influenza viruses or genetic excha...

#Pathogenicity and #transmissibility of bovine-derived HPAI #H5N1 B3.13 virus in #pigs

Abstract Since the first emergence of highly pathogenic avian influenza (HPAI) H5N1 viruses in dairy cattle , the virus has continued to spread, reaching at least 17 states and at least 950 dairy herds in the United States. Subsequently, spillovers of the virus from dairy cattle to humans have been reported. Pigs are an important reservoir in influenza ecology because they serve as a mixing vessel in which novel reassortant viruses with pandemic potential can be generated. Here, we show that oro-respiratory infection of pigs resulted in productive replication of a bovine-derived HPAI H5N1 B3.13 virus . Infectious virus was mainly identified in the lower respiratory tract of principal infected pigs, and sero-conversion was observed in most of the principal pigs at later time points, suggesting limited replication of the bovine-derived HPAI H5N1 B3.13 virus in pigs. In one animal, we detected the emergence of a mutation in hemagglutinin (HA) previously associated with increased affinity ...

Epitope-optimized #vaccine elicits enduring #immunity against swine #influenza A virus

Abstract Swine Influenza A Virus (IAV-S) poses a significant burden to both the pork industry and public health . Current vaccines against IAV-S are infrequently updated and induce strain-specific immunity. Computational platforms have recently emerged as a promising strategy to develop new-age vaccines. Here, we describe the Epigraph , a computationally derived and epitope optimized set of vaccine immunogens. When compared to wildtype immunogens (WT) and a commercial comparator (FluSure XP®), pigs immunized with Epigraph demonstrate significantly improved breadth and magnitude of antibody responses . Further, pigs immunized with Epigraph show more robust and a wider breadth of cross-reactive cell-mediated immune responses than pigs immunized with WT immunogens. In an experimental infection model , Epigraph immunized pigs demonstrate a significant reduction of clinical disease, lower shedding of infectious virus, reduction of lung lesions, and lower microscopic immunopathology compared...

Diverse #Genomic #Landscape of Swine #Influenza A Virus in #England (2014 - 2021)

Abstract Surveillance of influenza A viruses in pigs (SwIAV) is critical for identification of novel genetic groups that pose a risk to pig health and might have zoonotic potential . SwIAVs circulating in pigs in England between 2014 and 2021 were characterised using whole genome sequencing (WGS). Haemagglutinin (HA) and neuraminidase (NA) sequencing data from 82 of 368 influenza A positive samples (71 submissions) were determined, identifying H1N1 and H1N2 subtypes from the 1A classical swine and 1B human-seasonal lineages respectively. The 1B lineage viruses were predominant, accounting for 68.29% of sequenced viruses, with 1A lineage viruses comprising 31.71%, primarily from the 1A.3.3.2 clade (2009 H1N1 pandemic origin). This study characterised previously undefined diversity within the 1B lineage which led to the designation of new HA clades 1B.1.1.1, 1B.1.1.2 and 1B.1.1.3. Complete genome data were obtained from 64/82 viruses thereby updating the definition of genetic diversity t...

Circulation and #Spillover of #H1N1pdm09 #Influenza A Virus at an Educational #Swine #Farm in #Chile, 2019–2023

Abstract Educational farms provide students with hands-on experience in agricultural and animal practices . However, the close contact between humans and farm animals creates a significant interface for zoonotic disease transmission , yet research on infectious diseases in such settings remains limited. This study investigates the ongoing spillovers of human-origin influenza A virus (IAV) into swine at an educational farm in central Chile , describing IAV prevalence, outbreak dynamics, and the genomic characterization of detected strains. The Menesianos educational farm, located in Melipilla, central Chile, houses approximately 40 swine alongside other domestic animals , such as horses and cows . As part of an active IAV surveillance project, monthly nasal swab samples were collected from pigs between June 2019 and September 2023 for IAV detection via RT-qPCR targeting the M gene, with positive samples subsequently sequenced. During the study period, monthly IAV prevalence ranged from ...

High Prevalence of #Influenza D Virus #Infection in #Swine, Northern Ireland

Abstract We detected influenza D virus in multiple swine herds in Northern Ireland . Whole-genome sequencing showed several circulating genotypes and novel mutations in the receptor-binding site and esterase domains of the hemagglutinin-esterase fusion protein. Transmission routes of influenza D virus to swine remain to be clarified but could be direct or indirect. Source: US Centers for Disease Control and Prevention,  https://wwwnc.cdc.gov/eid/article/31/5/24-1948_article ____

Exploring influenza A virus receptor distribution in the lactating mammary gland of domesticated livestock and in human breast tissue.

Abstract The spread of the highly pathogenic avian influenza (HPAI) H5N1 virus among dairy cattle illustrates the adaptability of influenza A viruses (IAV) to infect non-traditional species . While IAV-specific sialic acid (SA) receptors have been identified in the mammary glands of dairy cattle , their presence in pigs, sheep, goats, and alpacas has not been studied until now. The zoonotic transmission of HPAI H5N1 to dairy and poultry farm workers during outbreaks raises public health concerns . This study employed lectin histochemistry to examine the mammary glands of livestock and humans . We found that these tissues were rich in SA α2,6-Gal receptors, followed by SA α2,3-Gal receptors , essential for IAV binding . Notably, the A(H5N1) clade 2.3.4.4b virus could bind to mammary tissue from both cattle and pigs . These findings highlight the potential for HPAI H5N1 to infect and spread within the mammary glands of production animals and humans. Source: BioRxIV,  https://www.bior...

Antigenicity and genetic #properties of an #Eurasian #avian-like #H1N1 swine #influenza virus in #Jiangsu Province, #China

Highlights •  Scientific question :  Cross-species transmission of influenza A viruses from swine to humans occurs occasionally because their tracheal epitheliums possess both sialic acid α-2,6-Gal and α-2,3-Gal receptors . In 2011, the first human case of swine influenza virus infection in the mainland of China was detected in Jiangsu Province . Subsequently, the Eurasian avian-like H1N1 swine influenza virus (EAH1N1 SIV) had sporadically crossed the host barrier and infected humans, raising public concern for its pandemic potential. •  Evidence before this study :  A/Jiangsu/1/2011 (H1N1v) was first discovered in 2011 and belongs to the G1 genotype. The G4 and G5 genotypes that appeared successively in 2013 are recombinant H1N1 swine influenza viruses. The EAH1N1 SIVs from 2016 to the present are dominated by the G4 genotype, with hemagglutination (HA) and neuraminidase (NA) genes derived from the EAH1N1 SIVs, non-structural protein (NS) genes derived from the trip...

A novel reassorted #swine #H3N2 #influenza virus demonstrates an undetected #human-to-swine #spillover in Latin #America and highlights zoonotic risks

Highlights •  First isolation and molecular evidence of the subtype H3N2 in swine in Colombia . •  Swine H3N2 discovered is phylogenetically divergent from other viruses. •  Colombian H3N2 was originated from an independent human-to-swine spillover. •  Sequence-based analysis reveals this is a novel antigenic variant . •  Due to antigenic variation , Colombian H3N2 possess a relevant zoonotic risk. Abstract Influenza A virus (FLUAV) affects a wide range of hosts, including humans and animals, posing a threat to public health . In swine, H3N2 subtype is associated with human-to-swine spillovers of seasonal viruses . In Latin America , the molecular and antigenic characteristics of swine FLUAV H3N2, as well as its phylogenetic origin, are poorly understood. Therefore, the objective of this study was to characterize the first swine H3N2 detected in Colombia . The origin and lineage of the virus were estimated through phylogenetic and molecular clock analyses . Anti...

#Pathogenicity and #transmissibility of #bovine-derived HPAI #H5N1 #B3.13 virus in #pigs

Abstract Since the first emergence of highly pathogenic avian influenza (HPAI) H5N1 viruses in dairy cattle , the virus has continued to spread, reaching at least 16 states and at least 950 dairy herds in the United States . Subsequently, spillovers of the virus from dairy cattle to humans have been reported. Pigs are an important reservoir in influenza ecology because they serve as a mixing vessel in which novel reassortant viruses with pandemic potential can be generated. Here, we show that oro-respiratory infection of pigs resulted in productive replication of a bovine-derived HPAI H5N1 B3.13 virus. Infectious viruses were mainly identified in the lower respiratory tract of principal infected pigs, and sero-conversion was observed in most of the principal pigs at later time points. In one animal, we detected the emergence of a mutation in hemagglutinin (HA) previously associated with increased affinity for mammalian-type alpha 2,6-linked sialic acid receptors , but this mutation did...

Rapid #Surge of #Reassortant A(#H1N1) #Influenza Viruses in Danish #Swine and their #Zoonotic Potential

Abstract In 2018, a single detection of a novel reassortant swine influenza A virus (swIAV) was made in Denmark . The hemagglutinin (HA) of the virus was from the H1N1 pandemic 2009 (H1N1pdm09) lineage and the neuraminidase (NA) from the H1N1 Eurasian avian-like swine lineage (H1N1av). By 2022, the novel reassortant virus (H1pdm09N1av) constituted 27% of swIAVs identified through the Danish passive swIAV surveillance program . Sequencing detected two H1pdm09N1av genotypes; Genotype 1 contained an entire internal gene cassette of H1N1pdm09 origin, Genotype 2 differed by carrying an NS gene segment of H1N1av origin . The internal gene cassette of Genotype 2 became increasingly dominant, not only in the H1pdm09N1av population, but also in other Danish enzootic swIAV subtypes. Phylogenetic analysis of the HA genes from H1pdm09N1av viruses revealed a monophyletic source , a higher substitution rate compared to other H1N1pdm09 viruses and genetic differences with human seasonal and other swi...

Reduction of #Influenza A Virus #Prevalence in #Pigs at Weaning After Using Custom-Made Influenza #Vaccines in the Breeding #Herds of an Integrated Swine #Farm System

Abstract Vaccination is a common influenza A virus (IAV) control strategy for pigs. Vaccine efficacy depends on strain cross-protection and effective vaccination program implementation. We evaluated a multi-faceted IAV vaccination strategy which included (a) monthly surveillance of pigs at weaning , (b) selection of epidemiologically relevant strains from farms under surveillance, (c) updating IAV strains in custom-made vaccines, and (d) seasonal mass vaccination with custom-made vaccines given to sows in 35 farrow-to-wean farms within an integrated swine farm system. Reduction of IAV in pigs from vaccinated sows was determined by monthly monitoring of farms for 30 months by IAV rRT-PCR (PCR) testing of nasal wipes collected from litters of piglets at weaning. Hemagglutinin (HA) nucleotide and amino acid (AA) sequence homology of the circulating and vaccine strains was determined by pairwise alignment and AA comparison at antigenic sites. Of the 35 farms monitored, 28 (80%) tested posi...

The #Swiss national #program for #surveillance of #influenza A viruses in #pigs and #humans: genetic variability and zoonotic transmissions from 2010 – 2022

Abstract Influenza A viruses (IAV) are likely candidates for pandemics . This report summarizes the results of the Swiss national program for surveillance of influenza viruses in pigs and transmissions to humans between 2010 and 2022. Challenges and optimization options in the program are discussed. Nasal swabs or lung tissue samples from pigs with influenza-like signs (e.g. fever, cough) were screened by real-time RT-PCR for swine influenza virus (SIV) genomes, including that of the 2009 pandemic strain A(H1N1)pdm09; positive samples were subtyped for H1, N1, H3 and N2 by RT-PCR and Sanger sequencing. In parallel, humans with influenza-like symptoms and recent contact to diseased pigs were asked to self-sample themselves with a nasal swab. Human swabs were tested for IAV and positive swabs further subtyped to identify potential cross-species transmission between swine and humans. In the pigs, SIV was detected in 375 of 674 farm visits . H1N1 is the only subtype detected in Swiss pigs ...

#Isolation and Characterization of #H1 Subtype #Swine #Influenza Viruses Recently Circulating in #China

Abstract Pigs serve as a mixing vessel for influenza viruses and can independently promote the emergence of pandemic strains in humans. During our surveillance of pig populations from 2021 to 2023 in China , 11 H1 subtype swine influenza viruses (SIVs) were isolated. All viruses were reassortants , possessing internal genes of identical origins ( PB2, PB1, PA, NP, M : pdm09/H1N1 origin, NS : North American triple reassortant origin). The H1N1 isolates were all the dominant G4 EA H1N1 viruses in China. Two H1N2 isolates carried early human pdm09/H1N1 HA genes, suggesting a possible pig-to-human transmission route. Mutations that dictate host range specificity were identified in all isolates, a phenomenon which may enhance the affinity to human receptors. These H1 subtype viruses effectively replicated both in vivo and in vitro without prior adaptation and exhibited different pathogenicity and growth characteristics. Some of the H1 viruses were even found to cause lethal infections in mi...

Novel introductions of #human-origin #H3N2 #influenza viruses in #swine, #Chile

Abstract Influenza A virus (IAV) continuously threatens animal and public health globally , with swine serving as a crucial reservoir for viral reassortment and evolution . In Chile , H1N2 and H3N2 subtypes were introduced in the swine population before the H1N1 2009 pandemic, and the H1N1 was introduced from the H1N1pdm09 by successive reverse zoonotic events . Here, we report two novel introductions of IAV H3N2 human-origin in Chilean swine during 2023. Our study reveals a closer relationship between recent human seasonal H3N2 and novel swine strains. Interestingly, one strain maintains all the genes from the original human virus , but the other strain is already a reassortment of human H3N2 and an H1N2 previously observed on the farm. Observing global IAV sequences, a similar pattern was identified in the USA confirming the reverse zoonotic potential of current seasonal human H3N2 strains. These results highlight the importance of ongoing surveillance and reinforcing biosecurity in ...

Phylogeographic Characterizations of Recent (2015–2023) #Senecavirus A Isolates from #Canada

Abstract Senecavirus A (SVA) continues to cause vesicular lesions in swine in Canada and many regions worldwide. Since the vesicular lesions caused by SVA are similar to those caused by foot and mouth disease virus , swine vesicular disease virus and vesicular stomatitis virus, a foreign animal disease investigation must be initiated to rule out these diseases. SVA isolates from pigs displaying vesicular lesions in Canada from 2015 to 2023 were sequenced, and phylogeographic analysis was performed using the complete genome sequences. The results infer that SVA has spread between the United States and Canada several times. In addition, the results suggest that SVA spreads from different regions. SVA spread was inferred from Canada into Thailand, India and Mexico and inferred from the United States to Brazil, Columbia, Chile and China with ten separate introductions. Furthermore, recombination was observed in SVA genomes from Canada, the United States and China. Source: Viruses,  htt...

Geographical #distribution and evolutionary #dynamics of #H4Nx avian #influenza viruses

Abstract H4Nx avian influenza viruses (AIVs) have been isolated from wild birds and poultry and can also cross the species barrier to infect mammals ( pigs and muskrats ). The widespread presence of these viruses in wild birds and poultry and their ability to be transmitted interspecies make them an undeniable hazard to the poultry farming industry. In the present study, we collected fecal and swab samples from wild birds and poultry in Guangdong Province from January 2019 to March 2024, and various subtypes of AIVs were isolated, including 19 strains of H4 subtype AIVs . Further analysis was conducted on the internal genes of the 19 strains . These strains clustered together with high homology to highly pathogenic avian influenza virus (HPAIV), suggesting that H4Nx AIV may be reassorted from HPAIV . Two H4N8 strains are phylogenetically related to the porcine H4N8 AIV. Molecular characterization revealed that all viruses in this study were less pathogenic but had potential mammalian-a...

Susceptibility of #bovine respiratory and mammary epithelial #cells to avian and #mammalian derived clade 2.3.4.4b #H5N1 highly pathogenic avian #influenza viruses

Abstract Zoonotic transmission of avian influenza viruses into mammals is relatively rare due to anatomical differences in the respiratory tract between species. Recently, clade 2.3.4.4b highly pathogenic H5N1 avian influenza viruses were detected circulating in North American cattle. Sporadic transmission between cattle, humans, and other animals proximal to cattle or after consuming products from infected cattle has occurred, but thus far there is no evidence of human-to-human transmission . However, the virus has the potential to adapt to the mammalian respiratory tract with every transmission event that occurs, making it crucial to understand cellular and species tropism of the H5N1 2.3.4.4b viruses. We compared viral kinetics of clade 2.3.4.4b viruses isolated from birds and mammals in respiratory epithelial cells derived from cattle, human, swine, and ferret. We found that avian derived viruses could replicate in swine cells only , yet mammalian derived strains could replicate ef...

#Zoonotic #transmission of novel #Influenza A #variant viruses detected in #Brazil during 2020 to 2023

Abstract Zoonotic infections (swine-human) caused by influenza A viruses (IAVs) have been reported and linked to close contact between these species . Here, we describe eight human IAV variant infections ( 6 mild and 2 severe cases , including 1 death ) detected in Paraná, Brazil , during 2020–2023. Genomes recovered were closely related to Brazilian swIAVs of three major lineages (1 A.3.3.2/ pdm09, 1B/human-like, and H3.1990.5), including three H1N1v, two H1N2v, two H3N2v and one H1v. Five H1v were closely related to pdm09 lineage , one H1v ( H1N2v ) grouped within 1B.2.3 clade, and the two H3v grouped within a clade composed exclusively of Brazilian H3 swIAV (clade H3.1990.5.1). Internal gene segments were closely related to H1N1pdm09 isolated from pigs . IAV variant rarely result in sustained transmission between people, however the potential to develop such ability is of concern and must not be underestimated. This study brings into focus the need for continuous influenza surveilla...