The #receptor binding properties of #H5Nx #influenza A viruses have evolved to promiscuously bind to avian-type mucin-like O-glycans

Abstract

Highly pathogenic H5Nx influenza A viruses are causing unprecedented, season-independent outbreaks across avian and mammalian species, including dairy cattle, a novel reservoir. The sialoside-binding properties of influenza A hemagglutinin (HA) are strongly related to its ability to infect and transmit between hosts. Mucin-like O-glycans, omnipresent in respiratory tracts, have been understudied as viral receptors due to their complexity. To address this, we synthesized 25 O-linked glycans with diverse sialosides, including modifications by fucosides and sulfates. Our findings reveal that H5Nx 2.3.4.4b viruses uniquely bind core 3 sialyl-Lewisx and Sia-Gal-β3GalNAc, glycans not recognized by classical H5 or other avian viruses. By determining its crystal structure, we resolved the structural features of both structures in an H5 hemagglutinin (HA) from a 2016 2.3.4.4b virus. While these viruses do not bind human-type receptors, their promiscuous receptor specificity enhances binding to human tracheal tissues, suggesting that O-glycan recognition contributes to their zoonotic potential.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.04.24.650378v1

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Emergence and interstate spread of highly pathogenic avian #influenza A(#H5N1) in dairy #cattle in #USA

Editor’s summary

High-pathogenicity avian influenza subtype H5N1 is now present throughout the US, and possibly beyond. More cattle infections elevate the risk of the virus evolving the capacity to transmit between humans, potentially with high fatality rates. Nguyen et al. show that from a single transmission event from a wild bird to dairy cattle in December 2023, there has been cattle-to-poultry, cattle-to-peridomestic bird, and cattle-to-other mammal transmission. The movement of asymptomatic dairy cattle has facilitated the rapid dissemination of H5N1 from Texas across the US. Evolution within cattle, assessed using deep-sequencing data, has detected low-frequency sequence variants that had previously been associated with mammalian adaptation and transmission efficiency. —Caroline Ash

Structured Abstract

INTRODUCTION

Highly pathogenic avian influenza (HPAI) viruses have critical consequences for animal health and the agricultural economy—and may have pandemic potential. HPAI related to the goose/Guangdong 2.3.4.4 hemagglutinin (HA) H5NX phylogenetic clade has spread to nearly 100 countries, and it is recognized as a panzootic. HPAI virus circulation is ongoing in North America, and after a trans-Atlantic incursion in late 2021, the HPAI H5N1 clade 2.3.4.4b virus caused widespread outbreaks. The outbreaks resulted in extensive mortality events, culling of poultry when detected in agricultural systems, and interspecies transmission events into mammals. It is critical to determine how HPAI clade 2.3.4.4b evolves in wild birds and in nonhuman mammals after spillover to assess the potential for human infection and transmission.

RATIONALE

In late January 2024, veterinarians observed dairy cattle displaying decreased feed intake and changes in milk quality and production. On 25 March 2024, HPAI H5N1 clade 2.3.4.4b was confirmed in dairy cattle in Texas. Shortly thereafter, the virus was identified in cattle in eight other United States (US) states by members of the National Animal Health Laboratory Network. The goal of this study was to analyze genetic sequence data collected after the introduction of HPAI H5N1 in late 2021 into the Atlantic flyway of North America and its onward circulation and reassortment with North American wild bird–origin low-pathogenicity viruses. These data were combined with whole-genome sequence data and epidemiological information from the HPAI H5N1 outbreak among US dairy cattle to help us understand when the interspecies transmission event to cattle occurred and the consequences of animal movement for virus spread.

RESULTS

H5N1 clade 2.3.4.4b genotype B3.13 influenza A virus was confirmed in milk with limited detections in nasal swabs. The initial outbreak included samples from 26 dairy cattle premises across eight states and six poultry premises in three states. The sequences isolated from cattle clustered within a single group in phylogenetic analyses, supporting a single spillover event in late 2023. A reassortment event preceded the spillover, and after introduction, the virus persisted in cattle with evidence for transmission from cattle into poultry and peridomestic animal species. Epidemiological records and phylodynamic modeling documented that the movement of asymptomatic or presymptomatic dairy cattle resulted in the dissemination of the virus across the US. We identified low-frequency within-host sequence variants across the genome that were associated with changes in virulence, host-range specificity, and mammalian adaptation.

CONCLUSION

A single wild bird-to-cattle transmission event of HPAI H5N1 clade 2.3.4.4b occurred in late 2023. The spillover was likely preceded by a reassortment event in wild bird populations followed by the movement of cattle that spread HPAI within the US dairy herd. Molecular markers that may lead to changes in transmission efficiency and phenotype were detected at low frequencies. Continued transmission of H5N1 HPAI within dairy cattle increases the risk for infection and subsequent spread of the virus to humans and other host populations.

Abstract

Highly pathogenic avian influenza (HPAI) viruses cross species barriers and have the potential to cause pandemics. In North America, HPAI A(H5N1) viruses related to the goose/Guangdong 2.3.4.4b hemagglutinin phylogenetic clade have infected wild birds, poultry, and mammals. Our genomic analysis and epidemiological investigation showed that a reassortment event in wild bird populations preceded a single wild bird–to-cattle transmission episode. The movement of asymptomatic or presymptomatic cattle has likely played a role in the spread of HPAI within the United States dairy herd. Some molecular markers that may lead to changes in transmission efficiency and phenotype were detected at low frequencies. Continued transmission of H5N1 HPAI within dairy cattle increases the risk for infection and subsequent spread of the virus to human populations.

Source: Science, https://www.science.org/doi/10.1126/science.adq0900

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#Seroprevalence of #H9N2 and #H5 avian #influenza in mixed-species #poultry #farms in Northern #Benin

ABSTRACT

Avian influenza is one of the major threats to poultry and human health in northern Benin, while mixed-species farming systems increase the risks of viral transmission. The present study estimated the seroprevalence of avian influenza subtypes H9N2 and H5 in indigenous chickens and guinea fowls in the Atacora and Donga regions. A total of 300 birds including 191 indigenous chickens and 109 guinea fowls, from six districts were sampled through a cross-sectional survey using systematic random sampling. Hemagglutination inhibition assay was used to detect antibodies, revealing an overall H9N2 seroprevalence of 41%, with 17.5% of samples testing positive for H5. The seroprevalence of H9N2 was notably higher in guinea fowls (51.81% in Atacora and 52% in Donga) compared to chickens (34.95% in Atacora and 34.83% in Donga). H5 antibodies were found only in guinea fowls in Atacora (46.66%). The study also found that farms with both chickens and guinea fowls had a significantly higher odds ratio for H9N2 positivity (OR = 4.25, p < 0.001) compared to chicken-only farms. The results underscore the importance of mixed-species systems in the transmission of avian influenza, suggesting that targeted surveillance and biosecurity measures are essential for controlling the spread of these viruses.

Source: Journal of Immunoassay and Immunochemistry, https://www.tandfonline.com/doi/full/10.1080/15321819.2025.2496480

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#Remdesivir, mAb114, REGN-EB3, and #ZMapp partially rescue nonhuman #primates infected with a low passage #Kikwit variant of #Ebola virus

Abstract

In 2018, a clinical trial of four investigational therapies for Ebola virus disease (EVD), known as the PALM trial, was conducted in the Democratic Republic of Congo. All patients received either the antiviral remdesivir (RDV) or a monoclonal antibody product: ZMapp, mAb114 (Ebanga), or REGN-EB3 (Inmazeb). The study concluded that both mAb114 and REGN-EB3 were superior to ZMapp and RDV in reducing mortality from EVD. However, the data suggested that some patients in the RDV and ZMapp groups might have been sicker at the time of treatment initiation. Here, we assessed the efficacy of each of these therapies in a uniformly lethal rhesus monkey model of EVD when treatment was initiated 5 days after Ebola exposure. Treatment with RDV, mAb114, REGN-EB3, and ZMapp each resulted in similar survival (approximately 40%). Survival was associated with circulating viral load at treatment initiation. A trend of more escape mutants in the GP1 and GP2 domains was observed for the mAb114 group. Our data show similar suboptimal efficacy of individual therapeutics in the uniformly lethal NHP model of EVD, supporting further clinical investigation of therapeutic combinations to maximize the overall therapeutic effect and improve patient outcomes, particularly for the treatment of advanced stage EVD.

Source: Nature Communications, https://www.nature.com/articles/s41467-025-59168-5

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Investigating #Factors Driving Shifts in #Subtype #Dominance within #H5Nx Clade 2.3.4.4b High-Pathogenicity Avian #Influenza viruses

Abstract

H5Nx clade 2.3.4.4b high-pathogenicity avian influenza viruses (HPAIVs) have decimated wild bird and poultry populations globally since the autumn of 2020. In the United Kingdom (UK) and in continental Europe, the H5N8 subtype predominated during the first epizootic wave of 2020/21, with few detections of H5N1. However, during the second (2021/22) and third (2022/23) epizootic waves, H5N1 was the dominant subtype. The rapid shift in dominance from H5N8 to H5N1 was likely driven by a combination of virological, immunological, and/or host-related factors. In this study, we compared viral fitness and immunological responses in ducks, a key reservoir species, using dominant genotypes of H5N1 (genotype AB) and H5N8 (genotype A) from the second wave. While viral shedding dynamics were similar for both viruses, H5N8 was more pathogenic. Antigenic analysis of post-infection duck sera revealed that the haemagglutinin (HA) protein was antigenically similar across clade 2.3.4.4b H5 HPAIVs, but neuraminidase (NA) proteins displayed different patterns of cross-reactivity. We also modelled a scenario where ducks were pre-exposed to H5N1 (genotype C) or H5N8 (genotype A) from the first wave and subsequently challenged with either homologous or heterologous subtypes from the second wave (genotype AB or A). Despite the absence of seroconversion, pre-exposure to different subtypes resulted in varying clinical outcomes following challenge. These findings indicate that both viral and immunological factors likely played significant roles in the emergence and spread of H5Nx HPAIVs in wild bird populations.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.04.23.650244v1

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Efficacy of #Baloxavir #Treatment in Preventing #Transmission of #Influenza

Abstract

Background

Baloxavir marboxil (baloxavir) rapidly reduces influenza virus shedding, which suggests that it may reduce transmission. Studies of treatment with neuraminidase inhibitors have not shown sufficient evidence that they prevent transmission to contacts.

Methods

We conducted a multicountry, phase 3b trial to assess the efficacy of single-dose baloxavir treatment to reduce influenza transmission from index patients to household contacts. Influenza-positive index patients 5 to 64 years of age were randomly assigned in a 1:1 ratio to receive baloxavir or placebo within 48 hours after symptom onset. The primary end point was transmission of influenza virus from an index patient to a household contact by day 5. The first secondary end point was transmission of influenza virus by day 5 that resulted in symptoms.

Results

Overall, 1457 index patients and 2681 household contacts were enrolled across the 2019–2024 influenza seasons; 726 index patients were assigned to the baloxavir group, and 731 to the placebo group. By day 5, transmission of laboratory-confirmed influenza was significantly lower with baloxavir than with placebo (adjusted incidence, 9.5% vs. 13.4%; adjusted odds ratio, 0.68; 95.38% confidence interval [CI], 0.50 to 0.93; P=0.01), with an adjusted relative risk reduction of 29% (95.38% CI, 12 to 45). The adjusted incidence of transmission of influenza virus by day 5 that resulted in symptoms was 5.8% with baloxavir and 7.6% with placebo; however, the difference was not significant (adjusted odds ratio, 0.75; 95.38% CI, 0.50 to 1.12; P=0.16). Emergence of drug-resistant viruses during the follow-up period occurred in 7.2% (95% CI, 4.1 to 11.6) of the index patients in the baloxavir group; no resistant viruses were detected in household contacts. No new safety signals were identified.

Conclusions

Treatment with a single oral dose of baloxavir led to a lower incidence of transmission of influenza virus to close contacts than placebo. (Funded by F. Hoffmann–La Roche and others; CENTERSTONE ClinicalTrials.gov number, NCT03969212.)

Source: The New England Journal of Medicine, https://www.nejm.org/doi/full/10.1056/NEJMoa2413156?query=TOC

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#Geographic and #age #variations in mutational processes in #colorectal #cancer

Abstract

Colorectal cancer incidence rates vary geographically and have changed over time1. Notably, in the past two decades, the incidence of early-onset colorectal cancer, affecting individuals under the age of 50 years, has doubled in many countries2-5. The reasons for this increase are unknown. Here, we investigate whether mutational processes contribute to geographic and age-related differences by examining 981 colorectal cancer genomes from 11 countries. No major differences were found in microsatellite unstable cancers, but variations in mutation burden and signatures were observed in the 802 microsatellite-stable cases. Multiple signatures, most with unknown etiologies, exhibited varying prevalence in Argentina, Brazil, Colombia, Russia, and Thailand, indicating geographically diverse levels of mutagenic exposure. Signatures SBS88 and ID18, caused by the bacteria-produced mutagen colibactin6,7, had higher mutation loads in countries with higher colorectal cancer incidence rates. SBS88 and ID18 were also enriched in early-onset colorectal cancers, being 3.3 times more common in individuals diagnosed before age 40 than in those over 70, and were imprinted early during colorectal cancer development. Colibactin exposure was further linked to APC driver mutations, with ID18 responsible for about 25% of APC driver indels in colibactin-positive cases. This study reveals geographic and age-related variations in colorectal cancer mutational processes, and suggests that early-life mutagenic exposure to colibactin-producing bacteria may contribute to the rising incidence of early-onset colorectal cancer.

Source: Nature, https://www.nature.com/articles/s41586-025-09025-8

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#HK CHP investigates severe #paediatric case of #COVID19 co-infected with human #metapneumovirus

{Excerpt}

The Centre for Health Protection (CHP) of the Department of Health today (April 23) received a report of a case of severe paediatric COVID-19 and human metapneumovirus (hMPV) infection and reminded the public to observe personal, hand and environmental hygiene at all times. High-risk individuals should receive a COVID-19 vaccination as soon as possible and receive booster doses at appropriate times to minimise the risk of serious complications and death after infection.

The case involves an eight-month-old girl with good past health, who developed a fever and runny nose since April 19 and sought medical attention from a private doctor the next day. She developed cough and shortness of breath on April 21 and sought medical attention from another private doctor. She attended the Accident and Emergency Department of Hong Kong Adventist Hospital – Tsuen Wan on April 22 and was transferred to the Paediatric Intensive Care Unit of Princess Margaret Hospital for treatment on the same day. Her respiratory specimen tested positive for SARS-CoV-2 virus and hMPV upon laboratory testing. The clinical diagnosis was COVID-19 co-infectedwith hMPV complicated with croup. She is still hospitalised and is in critical condition.

A preliminary investigation revealed that the patient had not received COVID-19 vaccine and had no travel history during the incubation period. Two of her household contacts had presented with respiratory symptoms and had recovered.

(...)

Source: Centre for Health Protection, HK PRC SAR, https://www.info.gov.hk/gia/general/202504/23/P2025042300628.htm

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Did #horses act as intermediate #hosts that facilitated the emergence of 1918 #pandemic #influenza?

Abstract

The ecological factors that led to the 1918 influenza pandemic remain unknown. We hypothesise that horses acted as intermediate hosts spreading a pre-pandemic avian-origin virus before 1918. This is supported by reports describing a large epizootic of unusually severe equine influenza beginning in 1915. Furthermore, the high horse demand during WWI resulted in one of the biggest equine mobilisations in North America between 1914 and 1918. This extensive movement of horses provided abundant opportunities for virus reassortment between pre-pandemic avian and human influenza viruses. Archived equine tissues or serum samples will be needed to test this hypothesis.

Source: Journal of Infectious Diseases, https://academic.oup.com/jid/advance-article-abstract/doi/10.1093/infdis/jiaf197/8115353?redirectedFrom=fulltext&login=false

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#Risk #assessment of 2024 #cattle #H5N1 using age-stratified #serosurveillance data

ABSTRACT

The highly pathogenic avian influenza virus A(H5N1) clade 2.3.4.4b has caused a human outbreak in North America since March 2024. Here, we conducted a serosurveillance study to determine the risk of A(H5N1) clade 2.3.4.4b (2024 cattle H5N1) to general population. In the initial screening of 180 serum specimens encompassing all age groups, 2.2% (4/180) had detectable neutralizing antibody (nAb) titers against reverse genetics-derived 2024 cattle H5N1, with all collected from older adults aged ≥60 years old. Further screening showed that 4.2% (19/450) of adults aged ≥60 years old had detectable nAb titers against the 2024 cattle H5N1. 80% (4/5) serum specimens with nAb titer of ≥40 had detectable HI titer, and there was a positive correlation between nAb titer and HA binding (r = 0.3325, 95% confidence interval 0.2477 to 0.4123; P < 0.0001). The nAb titer against seasonal H1N1 virus was 4.2-fold higher for ≥60 years old individuals with detectable H5N1 nAb titer than those ≥60 years old ones without (geometric mean titer: 89.3 [95% CI 42.9-185.7]) vs 21.3 [95% CI 17.3-26.1], P < 0.0001), but there was no statistically significant difference between H5N1 and H3N2 nAb titer. There was no difference in demographics, comorbidities and clinical frailty scores between individuals with detectable H5N1 nAb and those without. Our findings suggest that most individuals lack nAb response against 2024 cattle H5N1 and there is an urgency to develop and evaluate H5N1 vaccine or prophylactic monoclonal antibodies. Immune imprinting may be responsible for the cross neutralization between H5N1 and H1N1 among older adults.

Source: Emerging Microbes and Infections, https://www.tandfonline.com/doi/full/10.1080/22221751.2025.2497304

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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

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Clade Ia #Monkeypox Virus Linked to Sexual #Transmission, #DRC, August 2024

Abstract

Several concurrent mpox outbreaks are ongoing in the Democratic Republic of the Congo. We report a case of severe clade Ia mpox in an adult woman with indeterminate HIV status who died 16 days after symptom onset. She self-identified as a sex worker and had spent time in the capital city, Kinshasa.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/5/24-1690_article

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Mathematical #modelling of in vitro #replication dynamics for multiple highly pathogenic avian #influenza clade 2.3.4.4 viruses in #chicken and #duck cells

Abstract

The introduction and subsequent detection of highly pathogenic avian influenza (HPAI) in poultry is influenced by the virus replication fitness, transmission fitness, and virulence in poultry. These viral fitness parameters are important for implementing surveillance and control measures for poultry. This study investigates the potential application of an avian in vitro model using primary chicken embryo (CEF) and duck embryo fibroblasts (DEF) to identify the viral fitness for a reference panel of eight dominant HPAI clade 2.3.4.4 virus genotypes: four H5N1 viruses isolated between 2021 and 2024, as well as three H5N8 and one H5N6 virus isolated between 2014 and 2020. Infectious virus titre and cytopathogenicity were measured in the primary cell cultures over time and these data were analysed using a mathematical model which delineates cell populations into susceptible, latent, infectious, and dead compartments. In addition to obtaining traditional virological parameters such as peak virus replication and the time to 50% cell death, eight new parameters, key among those, the infecting time (tinf), generation time (tgen) and basic reproduction number (R0), were estimated using the mathematical model. Collectively, these parameters contribute to virus characterization, enhancing the resolution for comparing genetically similar viruses. This approach can allow for the evaluation of virus virulence, replication fitness, and, ideally, transmissibility fitness across different hosts. This study underscores the potential of integrating avian in vitro models with mathematical modeling and builds towards rapid risk assessments of novel HPAI viruses.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.04.22.649950v1

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Serologic #Surveillance for #Orthoflaviviruses and #Chikungunya Virus in #Bats and #Opossums in #Chiapas, #Mexico

Abstract

We performed serologic surveillance for selected arthropod-borne viruses (arboviruses) in bats and opossums in the Lacandona Rainforest, Chiapas, Mexico, in 2023–2024. Sera were collected from 94 bats of at least 15 species and 43 opossums of three species. The sera were assayed by the plaque reduction neutralization test (PRNT) for antibodies to eight orthoflaviviruses (dengue viruses 1–4, St. Louis encephalitis virus, T’Ho virus, West Nile virus, and Zika virus) and one alphavirus (chikungunya virus; CHIKV). Twelve (12.8%) bats and 15 (34.9%) opossums contained orthoflavivirus-specific antibodies. One bat (a Jamaican fruit bat) was seropositive for Zika virus, and 11 bats contained antibodies to an undetermined orthoflavivirus, as did the 15 opossums. All bats and most opossums seropositive for an undetermined orthoflavivirus had low PRNT titers, possibly because they had been infected with another (perhaps unrecognized) orthoflavivirus not included in the PRNTs. Antibodies that neutralized CHIKV were detected in three (7.0%) opossums and none of the bats. The three opossums had low CHIKV PRNT titers, and therefore, another alphavirus may have been responsible for the infections. In summary, we report serologic evidence of arbovirus infections in bats and opossums in Chiapas, Mexico.

Source: Viruses, https://www.mdpi.com/1999-4915/17/5/590

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#Lassa Virus #Infection of Primary #Human #Airway Epithelial Cells

Abstract

Lassa mammarenavirus (LASV), a member of the family Arenaviridae, is a highly pathogenic virus capable of causing severe systemic infections in humans. The primary host reservoir is the Natal multimammate mouse (Mastomys natalensis), with human infections typically occurring through mucosal exposure to virus-containing aerosols from rodent excretions. To better understand the molecular mechanisms underlying LASV replication in the respiratory tract, we utilized differentiated primary human airway epithelial cells (HAECs) grown under air–liquid interface conditions, closely mimicking the bronchial epithelium in vivo. Our findings demonstrate that HAECs are permissive to LASV infection and support productive virus replication. While LASV entry into polarized HAECs occurred through both apical and basolateral surfaces, progeny virus particles were predominantly released from the apical surface, consistent with an intrinsic apical localization of the envelope glycoprotein GP. This suggests that apical virus shedding from infected bronchial epithelia may facilitate LASV transmission via airway secretions. Notably, limited basolateral release at later stages of infection was associated with LASV-induced rearrangement of the actin cytoskeleton, resulting in compromised epithelial barrier integrity. Finally, we demonstrate that LASV-infected HAECs exhibited a pronounced type III interferon response. A detailed understanding of LASV replication and host epithelial responses in the respiratory tract could facilitate the development of targeted future therapeutics.

Source: Viruses, https://www.mdpi.com/1999-4915/17/5/592

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#Vietnam reported one additional #human #infection with avian #influenza virus A #H5N1 (HK CHP, April 22 '25)

Influenza A H5N1, New Cases reported, week 16/2025:

- Date: 18/04/2025;

- Country: Vietnam; 

- Province: Tay Ninh province, Ben Cau district; 

- Sex: Female;

- Age: 8; 

- Clinical condition: Serious;

- Subtype: H5N1.

(...)

Source: Centre for Health Protection, Hong Kong PRC SAR, https://www.chp.gov.hk/files/pdf/2025_avian_influenza_report_vol21_wk16.pdf

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Molecular and ecological #determinants of #mammalian #adaptability in avian #influenza virus

Abstract

The avian influenza virus (AIV) primarily affects birds and poses an increasing concern due to its growing adaptability to other hosts, heightening zoonotic risks. The adaptability is a key factor in AIV to infect multiple non-avian species, including humans, companion animals, aquatic mammals, carnivores, and other mammals. The virus is evolving through genetic mutations and reassortments, leading to the emergence of AIV strains with enhanced virulence and adaptability in mammals. This highlights the critical need to understand the genetic factors of AIV, including mutations in polymerase proteins, surface antigens, and other regulatory proteins, as well as the dynamics of AIV-host interactions and environmental factors such as temperature, humidity, water salinity, and pH that govern the cross-species adaptability of the virus. This review provides comprehensive insights into the molecular/genetic changes AIV undergoes to adapt in mammalian hosts including bovines, swine, equines, canines, and felines. The adaptive mutations in viral polymerase proteins, such as PB2-E627K, and receptor specificity shift facilitate the virus adaptability in mammals. Since AIVs interact with specific receptors on host cells, therefore the type and distribution of receptors are crucial in determining the host range of the virus and its adaptability by facilitating attachment and entry of the virus. This review examines sialic acid receptor distribution and binding patterns in various mammalian hosts, emphasizing how the presence and structure of specific receptors influence viral interaction, adaptation, and transmission. The review concludes that the differential distribution and expression of SA receptors are vital in the mammalian adaptability and tissue tropism of viral strains. Notably, during the adaptation to mammals, AIVs show a shift in preference from α-2,3 to α-2,6 receptors. This review further emphasizes the role of ecological determinants in the adaptation of viruses to mammalian hosts. Low temperatures, high humidity, and neutral to slightly acidic pH levels enhance virus stability, facilitating its persistence in the environment and spread among susceptible hosts. Overall, AIV remains a global health threat, necessitating coordinated efforts in research, surveillance, and public health strategies.

Source: Infection, https://link.springer.com/article/10.1007/s15010-025-02529-5

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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.biorxiv.org/content/10.1101/2025.04.16.649193v1

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#Wastewater #sequencing reveals the #genomic landscape of #Influenza A virus in #Switzerland

Abstract

Influenza A virus poses significant public health challenges, causing seasonal outbreaks and pandemics. Its rapid evolution motivates continuous monitoring of circulating influenza genomes to inform vaccine and antiviral development. Wastewater-based surveillance offers an unbiased, cost-effective approach for genomic surveillance. We developed a novel tiling amplicon primer panel that covers diversity of influenza A virus, targeting segments of the surface proteins HA, NA, and M of subtypes H1N1 and H3N2. Using this panel, we sequenced nucleic acid extracts from 59 Swiss wastewater samples collected at four locations during the 2022/2023 and 2023/2024 winter seasons. We found that wastewater-based abundance estimates of the dominant H1N1 clades correlated with clinical-based estimates in the 2023/2024 season. Furthermore, wastewater-based sequencing revealed mutations in vaccine and drug target sites, consistent with clinical data. Overall, we demonstrate the effectiveness of wastewater-based genomic surveillance of influenza A, including lineage identification and mutation tracking to inform vaccine and antiviral strategies

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2025.04.17.25325990v1

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Impacts of high pathogenicity avian #influenza #H5N1 2.3.4.4b south of the #Antarctic Circle

Abstract

High pathogenicity avian influenza (HPAI) H5N1 2.3.4.4b poses a substantial conservation threat to ecosystems, populations, and species globally, with its continued spread into new regions increasing concern for potential ecological consequences. During surveys in February-March 2025, we confirmed the virus presence at the southern extent of its known range along the Western Antarctic Peninsula, with recorded mortalities in South Polar Skuas Stercorarius maccormicki on distinct islands in Marguerite Bay, as well as one confirmed and one suspected case in Kelp Gulls Larus dominicanus. At the time of sampling, no evidence of infection was observed in other seabird or mammal species. Consistent with previous global reports, skuas - here, South Polar Skuas - appear particularly vulnerable, yet broader impacts on the local seabird and mammal community remain unclear. Additionally, our use of rapid antigen tests (VDRG AIV Ag Rapid kit 2.0 Median Diagnostics) in the field demonstrated their potential utility for real-time surveillance, though false negatives (10%) highlight limitations in test sensitivity. These findings contribute to a growing understanding of the impacts of HPAI -H5N1 2.3.4.4b outbreaks on Antarctic species and populations, and will inform continued monitoring, conservation strategies, and biosecurity measures in response to the virus's ongoing spread.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.04.13.648652v1

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