Characterisation of a novel #chicken-derived #H3N3 avian #influenza virus detected in #China in 2023: Pathogenicity and immunogenicity

 

Abstract

The poultry industry faces a constant threat from the mutation and transmission of avian influenza viruses (AIVs). While waterfowl and wild birds are natural hosts of H3N3 AIV, reports of H3N3 infections in chickens are limited. However, in 2023, a decline in egg production among laying hens in the Yancheng Region of Jiangsu Province prompted a study. This research aimed to diagnose the aetiology in laying hens through molecular virological methods and characterise the biological properties of the causative pathogens. An H3N3 AIV subtype strain, A/chicken/China/YC01/2023(H3N3), was isolated from chickens exhibiting lesions. Genome sequencing and analysis revealed a novel genetic makeup: the HA gene originated from an H3N8 AIV, the NA gene from an H10N3 AIV, and the internal genes from an H9N2 AIV, all circulating in China. Chickens experimentally infected with the isolate showed signs of Harderian gland haemorrhage, nasal mucus, tracheal circumferential bleeding, and lung bleeding and localised necrosis. Histopathological examination confirmed nasal mucosal and tracheal inflammation, lung capillary congestion, liver cell damage, and sparse splenic lymphocytes. Viral shedding was significantly higher in the oropharyngeal cavity, peaking 2–6 days post-infection, compared to the cloaca. For the first time, the immunogenicity of a novel chicken-derived H3N3 subtype AIV was assessed in specific pathogen-free chickens. An inactivated vaccine, prepared from the isolated strain, resulted in antibody titres peaking at 9.6 log2 four weeks after immunization. Furthermore, challenges with either the isolated strain or a duck-origin BZ01/2023(H3N3) strain after immunisation did not cause clinical signs or viral shedding on day 4. In conclusion, the isolate H3N3 AIV can replicate in chickens, leading to organ damage and pathogenicity. Crucially, the inactivated vaccine derived from this isolate is highly immunogenic and provides cross-protection against the duck-derived strain.

Source: PLoS One, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0332213

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The identification and genetic characteristics of the #Orf #virus strain (ORFV-CL24) isolated from #Jilin province, #China

 

Abstract

Orf virus (ORFV), the prototype species of the Parapoxvirus genus within the Poxviridae family (subfamily Chordopoxvirinae), is a global pathogen infecting sheep, goats, and other ruminants, with zoonotic potential for humans. In this study, an outbreak of ORFV infection occurred in a sheep flock in Changling County, Jilin province, China, causing papules, pustules, and crusting lesions on the lips and eyelids. Typical parapoxvirus particles were observed using electron microscopy, and a wild ORFV strain was isolated, characterized, and designated as ORFV-CL24. To clarify the epidemiological and genomic characteristics of ORFV in the region, we completed its whole-genome sequencing (GenBank accession number: PV126639). Genome analysis revealed that ORFV-CL24 shares a conserved structure with other isolates available in GenBank, which possess a complete genomic sequence of 138,500 bp of dsDNA harboring 131 putative open reading frames (ORFs) flanked by inverted terminal repeat (ITR) regions of 3,264 bp at both termini. Additionally, the genome exhibited high GC-content (63.3%), indicating its key role in DNA stability. Phylogenetic analysis placed the wild strain within a subclade with the attenuated ORFV strain D1701, implying a putative common ancestor or epidemiological linkages. Further analysis of B2L (ORFV 011) and E3L (ORFV 020) genes further revealed genetic diversity and evolutionary patterns. Notably, despite phylogenetic relatedness, specific mutations in ORF020 further distinguished ORFV-CL24 from D1701, reflecting stepwise mutation accumulation during host adaptation. In conclusion, our results provided valuable genetic insights into ORFV-CL24, which contributed to a better understanding of its evolution, biological properties, and endemic trends in China.

Source: Frontiers in Microbiology, https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2025.1658326/full

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#WHO #statement on #autism-related issues (September 23 '25)

 

The World Health Organization (WHO) emphasizes that there is currently no conclusive scientific evidence confirming a possible link between autism and use of acetaminophen (also known as paracetamol) during pregnancy. 

Globally, nearly 62 million people (1 in 127) have autism spectrum disorder, a diverse group of conditions related to development of the brain. Although awareness and diagnosis have improved in recent years, the exact causes of autism have not been established, and it is understood there are multiple factors that can be involved.  

Extensive research has been undertaken over the past decade, including large-scale studies, looking into links between acetaminophen use during pregnancy and autism. At this time, no consistent association has been established. 

WHO recommends that all women continue to follow advice of their doctors or health workers, who can help assess individual circumstances and recommend necessary medicines. Any medicine should be used with caution during pregnancy, especially in the first three months, and in line with advice from health professionals. 

Also, a robust, extensive evidence base exists showing childhood vaccines do not cause autism. Large, high-quality  studies from many countries have all reached the same conclusion. Original studies suggesting a link were flawed and have been discredited. Since 1999, independent experts advising WHO have repeatedly confirmed that vaccines—including those with thiomersal or aluminum—do not cause autism or other developmental disorders.   

Childhood vaccine schedules are developed through a careful, extensive and evidence-based process involving global experts and country input. The childhood immunization schedule, carefully guided by WHO, has been adopted by all countries, and has saved at least 154 million lives over the past 50 years. The schedule remains essential for the health and wellbeing of every child and every community. These schedules have continually evolved with science and now safeguard children, adolescents and adults against 30 infectious diseases.  

Every vaccine recommendation by the Strategic Advisory Group of Experts on Immunization (SAGE), an independent advisory group to WHO, is grounded in rigorous review of evidence and carefully designed to offer the best protection against serious diseases and to be delivered when most needed.   

When immunization schedules are delayed or disrupted, or altered without evidence review, there is a sharp increase in the risk of infection not only for the child, but also for the wider community. Infants too young to be vaccinated and people with weakened immune systems or underlying health conditions are at greatest risk.  

Autism and neurodevelopmental disorders are among priority mental health and neurological conditions being discussed at the 4th UN High-Level Meeting on NCDs and mental health this Thursday, 25 September.  As a global community, we need to do more to understand the causes of autism and how best to care for and support the needs of autistic people and their families.   

WHO is committed to advancing this goal working together with partners including autistic-led organizations and other organizations representing persons with lived experience. WHO also stands with people who are living with autism and their families, a dignified community entitled to evidence-based considerations free of stigma.

Source: World Health Organization, https://www.who.int/news/item/24-09-2025-who-statement-on-autism-related-issues

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The #hemagglutinin proteins of clades 1 and 2.3.4.4b #H5N1 highly pathogenic avian #influenza viruses exhibit comparable attachment patterns to avian and #mammalian #tissues

 

ABSTRACT

The global spread of the A/goose/Guangdong/1/96-lineage H5N1 highly pathogenic avian influenza (HPAI) viruses has been accompanied by an expanded host range and the establishment of sustained viral transmission among dairy cattle. To evaluate if the evolving H5N1 viruses have changed tissue tropism over time, we compared the binding patterns of recombinant hemagglutinin (HA) proteins derived from clade 1 (A/Vietnam/1203/04, H5VN) and circulating clade 2.3.4.4b viruses detected from wild bird (A/Eurasian Teal/Hong Kong/AFCD-HKU-23-14009-01020/2023, H5HK) and dairy cattle (A/bovine/Ohio/B24OSU-439/2024, H5OH). The HA protein of A(H1N1)pdm09 virus was included for comparison. Using bio-layer interferometry, H1 protein preferentially bound to the α2,6-linked sialoside 6′SLNLN, while H5 proteins preferentially bound to the α2,3-linked sialoside 3′SLN. H5OH showed higher binding affinity to 3′SLN than H5HK and H5VN. The attachment patterns of H1 and H5 proteins to the respiratory tissues of different species and dairy cattle mammary glands were evaluated. Compared to the H1 protein, H5 proteins showed stronger binding to the lung epithelial cells of cat, cattle, chicken, ferret, human, and pig, and the clade 2.3.4.4b H5 proteins exhibited increased binding to pig and cattle bronchial epithelial cells. All H5 proteins were attached to the alveolar and cistern epithelial cells in mammary glands, where α2,3-linked and α2,6-linked sialyl glycans were detected by Maackia amurensis lectin II and Sambucus nigra lectin, respectively. Taken together, the HA proteins of clade 1 and 2.3.4.4b H5N1 viruses generally share comparable attachment patterns to avian and mammalian tissues, despite evolving into antigenically distinct clades over the past 3 decades.

IMPORTANCE

The outbreaks of H5N1 highly pathogenic avian influenza (HPAI) virus among US dairy cattle since 2024 have raised concerns of the potential changes in HA receptor binding specificity and tissue tropism. Using insect-cell-expressed recombinant HA proteins derived from clade 1 and circulating clade 2.3.4.4b H5N1 viruses, we showed that the dairy cattle H5 protein retained binding specificity for the avian-like α2,3-linked sialoside 3′SLN over the human-like α2,6-linked sialoside 6′SLNLN, with higher binding affinity to 3′SLN than the other H5 proteins. Clade 1 and 2.3.4.4b H5 proteins showed comparable attachment patterns to the mammary tissues of lactating dairy cattle, which showed high expression of α2,3-linked and α2,6-linked sialyl glycans. All H5 proteins also showed comparable attachment patterns to the lungs of cat, cattle, chicken, ferret, human, and pig. Our results suggest that the recent H5N1 outbreaks in dairy cattle may be related to ecological factors rather than changes in HA receptor binding specificity.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.00976-25?af=R

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#Human #metapneumovirus: understanding the molecular mechanisms and #pathology of #infection

 

ABSTRACT

Human metapneumovirus (HMPV) is a common and globally prevalent respiratory virus that can cause clinical symptoms ranging from mild respiratory illness to severe bronchiolitis and pneumonia, with substantial morbidity and mortality. HMPV accounts for a substantial health care and economic burden, with high hospitalization rates. Consequently, there is an urgent need for effective preventive and therapeutic interventions. The development of these interventions requires comprehensive knowledge of the virus’s biology, including characteristics, epidemiology, evolution, virus-host interactions, and host immune responses. Despite being discovered nearly 25 years ago, HMPV has remained relatively underrecognized, resulting in limited awareness of its true impact and delays in the development of treatment options. Recent studies have demonstrated the emergence of novel genotypes and provided more insight into viral replication, spread, and host immune responses. In this review, we highlight the clinical significance of HMPV and explore the molecular mechanisms the virus employs throughout the course of an infection.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.00284-25?af=R

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Broadly #Sarbecovirus-Neutralizing #Antibodies Induced by Ancestral #SARS-CoV-2 #Infection

 

Abstract

The COVID-19 pandemic, driven by SARS-CoV-2, continues to challenge global health due to emerging variants and the potential risk posed by related sarbecoviruses. Neutralizing antibodies targeting the spike (S) glycoprotein, particularly the receptor-binding domain (RBD), play a crucial role in viral neutralization and vaccine design. Although broadly neutralizing anti-RBD antibodies have been identified, the nature of cross-reactive humoral responses induced by natural infection with ancestral SARS-CoV-2 strains remains incompletely understood. Here, we isolated 105 S-specific monoclonal antibodies (mAbs) from individuals recovered from prototype SARS-CoV-2 infection. Of these, 30 mAbs cross-recognized SARS-CoV-1, including 25 RBD-directed mAbs, of which 12 displayed cross-neutralizing activity against both viruses. Among them, mAb 12C2 potently neutralized SARS-CoV-1 and multiple SARS-CoV-2 variants, likely through mechanisms that include inhibition of membrane fusion and potential destabilization of the S trimer. Cryo-electron microscopy revealed that 12C2 engages the outer face of the RBD, overlapping with the epitope recognized by the broadly neutralizing antibody S309 derived from SARS-CoV-1 convalescent. Collectively, these findings demonstrate that ancestral SARS-CoV-2 infection can elicit robust cross-neutralizing antibody responses and provide valuable insights for the design of broadly protective antibodies and vaccines.

Source: Viruses, https://www.mdpi.com/1999-4915/17/10/1285

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From #zoonotic #spillover to endemicity: the broad determinants of #human #coronavirus tropism

 

ABSTRACT

Given the recurring threat of coronavirus outbreaks, understanding the specificity of coronaviruses in terms of their host, tissue, and cell tropism is crucial. This review consolidates and critically assesses the current literature on the tropism of endemic, epidemic, and pandemic coronaviruses. We explore different levels of tropism, including species tropism (virus preference for specific host species), host cell tropism (virus specificity for particular cell types), and tissue tropism (specificity for certain tissues or organs). This review compiles extensive basic research, particularly from recent years, to provide critical insights into the viral mechanisms that are key to improving future pandemic preparedness.

Source: mBio, https://journals.asm.org/doi/10.1128/mbio.02437-25

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#Global #epidemiology and public health #challenges of #MERS #Coronavirus

 

Highlights

• Middle East respiratory syndrome-coronavirus was first detected in 2012 in Saudi Arabia.

• Since 2012, Middle East respiratory syndrome caused 2626 confirmed cases.

• 20% of cases involve contact with dromedary camels or their products.

• Human-to-human spread occurs, mainly in healthcare settings.

• A case fatality rate is 36-40%.

Source: IJID Regions, https://www.sciencedirect.com/science/article/pii/S2772707625001663?via%3Dihub

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#Genomic #surveillance and #evolution of co-circulating avian #influenza #H5N1 and #H5N8 viruses in #Egypt, 2022–2024

 

ABSTRACT

For over two decades, avian influenza virus (AIV) has significantly impacted the Egyptian poultry population, with multiple subtypes and genotypes contributing to significant economic and agricultural losses. As part of an ongoing national surveillance effort, this study aimed to monitor and genetically characterize AIV circulation across various poultry sectors in Egypt. Between 2022 and 2024, a total of 446,790 swab samples were collected, representing commercial farms (n = 25,057), backyard flocks (n = 403), and live bird markets “LBM” (n = 1250) to assess the prevalence and genetic diversity of circulating AIV strains. A total of 173 sampling units were found positive for high pathogenicity (HP) AIV H5, including farms (n = 17), backyards (n = 11), and LBMs (n = 145). The HPAIV of H5N8 subtype was dominant (n = 75) over the H5N1 (n = 27) subtypes among all sectors and bird species (chickens, ducks, turkeys). Whole genome sequence analysis of positive H5 samples revealed high similarity with HPAIVs of clade 2.3.4.4b, which has been confirmed phylogenetically. Two distinct subtypes H5N1 (EA-2021-AB genotype) and H5N8 (EA-2020-A genotype) were identified, with two variants detected within the H5N8 viruses. Evolutionary analyses indicate that Egyptian H5N8 viruses are under strong selection pressure and exhibit a higher nucleotide substitution rate compared to the Egyptian H5N1 viruses of clade 2.3.4.4b. With the evolving HPAI H5 virus’s situation in different locations around the globe, including Egypt, this study underlines the importance of active surveillance in the timely detection of emerging AIV genotypes, monitoring virus evolution, and refining risk assessments.

Source: Emerging Microbes and Infections, https://www.tandfonline.com/doi/full/10.1080/22221751.2025.2562046#abstract

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#Poland - High pathogenicity avian #influenza #H5N1 viruses (#poultry) (Inf. with) - Immediate notification

Poultry farms in Warmińsko-Mazurskie Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6807

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Impaired host shutoff is a #fitness cost associated with #baloxavir marboxil #resistance mutations in #influenza A virus PA/PA-X nuclease domain.

 

Abstract

The polymerase acidic (PA) protein is a subunit of the trimeric influenza A virus (IAV) RNAdependent RNA polymerase and the target of the anti-influenza drug baloxavir marboxil (BXM). As with other direct-acting antivirals, treatment with BXM can lead to selection of viruses carrying resistance mutations. If these mutations have negligible fitness costs, resistant viruses can spread widely and render existing treatments obsolete. Multiple BXM resistance mutations in the nuclease domain of PA have been identified, with I38T and I38M amino acid substitutions occurring frequently. These mutations have minimal to no effects on viral polymerase activity, virus replication, or transmission. However, for reasons that are not well understood, viruses with BXM resistance substitutions have not been able to compete with parental wild-type strains. The IAV genome segment encoding PA also encodes the host shutoff nuclease PA-X, which shares the endonuclease domain with PA but has a unique C-terminal domain generated by ribosomal frameshifting during translation. Unlike their effects on PA activity, the effects of BXM or the I38T/M substitutions on PA-X function remain uncharacterized. In our work, for the first time, we directly examine the effects of baloxavir and the I38T/M substitutions on PA-X activity and show that baloxavir inhibits PA-X activity in a dose dependent manner. Most importantly, we also demonstrate that the I38T/M mutations significantly impair the host shutoff activity of PA-X proteins from different IAV strains of H1N1, H3N2, and H5N1 subtypes. Our work reveals that the deleterious effects of I38T/M on PA-X function may represent an important barrier to the spread of BXM-resistant viruses.

Competing Interest Statement

The authors have declared no competing interest.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.09.22.677688v1

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Dual-Route #H5N1 #Vaccination Induces Systemic and #Mucosal #Immunity in Murine and Bovine Models

 

Abstract

Since its discovery in U.S. dairy cattle in early 2024, the highly pathogenic H5N1 avian influenza (clade 2.3.4.4b) has spread widely among herds, causing major economic losses. This zoonotic event emphasizes the urgent need for H5 vaccines that elicit strong, durable, cross-reactive immune responses in cattle, especially young calves. To address this, we immunized mice and cattle with a centralized consensus H5 vaccine, designed to localize to the central node of the human H5 phylogenetic tree. The vaccine was delivered using serotype-switched adenoviral vectors in a prime:boost regimen, combined with intramuscular and intranasal coadministration to target systemic and mucosal immunity and elicit strong humoral and cellular immune responses. This approach strategically integrates multiple innovative features: centralized consensus immunogens, mucosal targeting, and vector serotype switching that are aimed at maximizing immune protection against H5N1 viruses. Our results show that vaccination elicited strong humoral and cellular immunity in both mice and calves. In challenge experiments, vaccinated mice were fully protected against lethal infection with multiple divergent H5N1 strains, including the 2024 bovine isolate (A/bovine/Ohio/B24OSU-439/2024). Given that vaccine induced immunity was consistent across species, these results support the translatability of the mouse model findings to cattle. Overall, our findings represent a promising approach for immunizing cattle and other key livestock against HPAI H5N1, mitigating agricultural losses, and reducing the risk of zoonotic transmission.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

National Institute of Food and Agriculture, 2020-06448, 2024-08723

NIH - NIAID, R01AI147109

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.09.21.677614v1

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Cross-reactive #neuraminidase inhibition #antibodies against #H5N1 by consecutive #influenza A imprinting cohorts of the past century: population-based serosurvey, British Columbia, #Canada

 

Abstract

Background: 

Avian influenza of the H5N1 subtype shares substantial relatedness in its neuraminidase (NA) surface protein with human influenza A H1N1 viruses of the past century. Understanding variation in pre-existing anti-N1 antibodies against H5N1 is critical to pandemic risk assessment and preparedness. 

Methods: 

We used anonymized, residual sera collected equally from ten age groups spanning one to >80 years during an August 2024 cross-sectional serosurvey in British Columbia, Canada. We assessed NA inhibition antibody titres by enzyme-linked lectin assay against H5N1 (N=575), H1N1pdm09 (N=250) and H3N2 (N=205). We compared anti-NA titres by birth (imprinting) cohorts defined in relation to historic N1 and/or N2 exposure opportunities. 

Results: 

Among participants with median age 32 (IQR: 15-62) years, 404 (70%) had cross-reactive anti-N1 titre ≥10 against H5N1, with 260 (45%), 182 (32%) and 98 (17%), having titres ≥40, ≥80 and ≥160, respectively. H5N1 titres were consistently lower but strongly associated with H1N1pdm09 (r=0.86; 95%CI:0.82-0.89). Geometric mean titres against H1N1pdm09 and H5N1 peaked among young adults born 1997-2003 (427.9, 100.8), declining to lows among young children born 2015-2023 (20.7, 6.8) and middle-aged adults born 1957-1967 (25.1, 10.7), increasing to similar secondary peak among older adults born pre-1947 (387.3, 81.0). 

Conclusions: 

A substantial proportion of the population has pre-existing, cross-reactive anti-N1 antibodies against H5N1. We interpret variation by age and imprinting cohorts within a unifying hypothesis, emphasizing the role of historic influenza pandemics in expanding and refining the immune repertoire through heightened attack rates and shifts in immunological hierarchies. Our findings have implications for H5N1 and other zoonotic influenza risk assessment.

Competing Interest Statement

DMS is Principal Investigator on grants received to her institution from the Public Health Agency of Canada, Pacific Public Health Foundation, Canadian Institutes of Health Research and the Michael Smith Foundation for Health Research for unrelated work. As the Provincial Health Officer with authority under the emergency provisions of the Public Health Act, BH authorized the provision and analysis of the anonymized sera used in this study; the study was separately reviewed and approved by the UBC Clinical Research Ethics Board and Health Canada-Public Health Agency of Canada Research Ethics Board. No other competing interests were declared.

Funding Statement

This work was supported by the Public Health Agency of Canada (Grant number: 2021-HQ-00067), received by the Institution of DMS. The views expressed herein do not necessarily represent the views of the Public Health Agency of Canada.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2025.09.19.25336209v1

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#Outbreak #dynamics of high pathogenicity avian #influenza virus #H5N1, clade 2.3.4.4b euBB, in black-headed #gulls and common #terns in #Germany in 2023

 

Abstract

Since winter 2022/23, high pathogenicity avian influenza virus (HPAIV) H5N1 clade 2.3.4.4b, genotype euBB, has caused extensive mortality among wild birds. This genotype emerged in France in spring 2022 through reassortment between a gull-adapted low-pathogenicity virus and HPAIV H5N1. Phylogeographic and spatiotemporal analyses show that transmission into German breeding colonies of black-headed gulls (Chroicocephalus ridibundus) and common terns (Sterna hirundo) involved multiple independent incursions, likely via black-headed gulls returning from wintering grounds in the Netherlands, Belgium, and France. It spilled over into common terns, which breed in shared colonies with black-headed gulls, and led to high adult mortality in both species in 2023 (at least 8,137 black-headed gulls and 614 common terns; >3% of the breeding population), followed by significant breeding pair declines in 2024 (-15.9% in black-headed gulls, -5.8% in common terns). Increased immunity, at least in common terns, may have contributed to the apparent fade-out of genotype euBB. These findings highlight how integrating ornithological, epidemiological, and virological data can aid our understanding of viral transmission routes and population-level impacts, while also stressing that HPAIV should be added to the growing list of pressures on seabirds, a group that was already the most threatened among all bird taxa globally.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

European Union, https://ror.org/019w4f821, 101084171

German Ornithological Society, DE

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.09.17.676714v1

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Still life with meadow flowers and roses, Vincent van Gogh (1886)

 

Public Domain.

Source: WikiArt, https://www.wikiart.org/en/vincent-van-gogh/still-life-with-meadow-flowers-and-roses-1886

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Developing and #Benchmarking #OneHealth #Genomic #Surveillance Tools for Influenza A Virus in #Wastewater

 

Abstract

Influenza A viruses (IAV) remain a persistent One Health threat, and whole-genome sequencing from wastewater offers a promising surveillance tool. However, IAV is at low abundance in wastewater, making it difficult to sequence. We benchmarked four targeted enrichment methods suited for whole-genome sequencing including custom and off-the-shelf amplicon and probe-based methods. Our custom HA tiled-amplicon panel was sensitive, fast, and cost-effective, making it suitable for monitoring low-abundance seasonal variants of known subtypes. However, its reliance on conserved and intact primer-binding sites limited primer design to fewer subtypes. A previously published universal amplicon method targeted all IAV subtypes, but it performed poorly in wastewater due to its reliance on intact genome segments. Probe-capture methods were resilient to RNA degradation and mismatches, potentially enabling broader surveillance and detection of emerging strains. However, probes were costly, labor-intensive, and less sensitive than tiled-amplicon. When testing compatibility of sequencing methods with upstream virus concentration and extraction methods, ultrafiltration-based virus concentration outperformed large-volume direct extraction with all four sequencing methods. This set of benchmarking comparisons and custom panels provides needed information for the translation of IAV genomic sequencing into a routine component of wastewater surveillance.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

University of California, Berkeley, L22CR4507

NIH Common Fund, 4R00GM144747-03

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.09.19.676942v1

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Non-neutralizing #antibodies to #influenza A #matrix-protein-2-ectodomain are broadly effective #therapeutics and resistant to viral escape mutations

 

Abstract

Influenza A viruses remain a global health threat, yet no universal antibody therapy exists. Clinical programs have centered on neutralizing mAbs, only to be thwarted by strain specificity and rapid viral escape. We instead engineered three non-neutralizing IgG2a mAbs that target distinct, overlapping epitopes within the conserved N terminus of the M2 ectodomain (M2e). Combined at low dose, this “triple M2e-mAb” confers robust prophylactic and therapeutic protection in mice challenged with diverse human and zoonotic IAV strains, including highly pathogenic variants. Therapeutic efficacy depends on Fc-mediated effector activity via FcγRI, FcγRIII, and FcγRIV, rather than in vitro neutralization. Serial passaging in triple M2e-mAb–treated immunocompetent and immunodeficient hosts failed to generate viral escape mutants. Our findings redefine the influenza-specific antibody therapeutic design and support Fc-optimized, non-neutralizing M2e-mAbs as a broadly effective, mutation-resistant, off-the-shelve therapy with direct relevance to human pandemic preparedness.

Source: Science Advances, https://www.science.org/doi/10.1126/sciadv.adx3505

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A case of #H10N3 avian #influenza in a young woman

 

Context and significance

The avian influenza A virus subtype H10N3 is a possible candidate for causing a fatal flu and may present a serious public health threat. Research increasingly shows that the avian influenza virus H10N3 can be transmitted from birds to humans, causing severe viral pneumonia and potentially leading to acute respiratory distress syndrome and respiratory failure. Researchers at the Fourth People’s Hospital of Nanning (China) provide evidence supporting the cross-species transmission of the avian influenza virus H10N3 to humans, which can give rise to severe pneumonia. The authors report that a female patient with avian influenza virus H10N3 infection, who was suffering from severe pneumonia, respiratory failure, pneumothorax, and numbness and dysesthesia in her feet, recovered after receiving appropriate therapy and was discharged from the hospital.

Highlights

• A young woman contracted the avian influenza virus H10N3

• Secondary infections, pneumothorax, and foot numbness developed consecutively

• Baloxavir marboxil and oseltamivir were administered

Summary

Background

Avian influenza viruses, frequently identified in wild waterfowl and poultry, have occasionally been transmitted to humans, causing severe respiratory diseases. This report covers the fourth case of a human contracting the H10N3 subtype of avian influenza virus.

Methods

A case of novel avian influenza virus subtype H10N3 was detected in a female patient hospitalized in Nanning, China, in December 2024. Blood, feces, urine, and bronchoalveolar lavage fluid were collected from the patient for medical analysis during the hospitalization.

Findings

A case of novel avian influenza virus subtype H10N3 was detected in a female patient hospitalized in Nanning, China, in December 2024. She also had a history of exposure to live poultry. This case represents the fourth documented instance of H10N3 infection in humans. She was treated with a combination of baloxavir marboxil and oseltamivir. She exhibited extensive lung lesions. Additionally, she presented complicating factors, including secondary infection, pneumothorax, and numbness in her feet. She recovered and was discharged on March 27, 2025, amid comprehensive supportive care, which included therapy with baloxavir marboxil, oseltamivir, fluconazole, tigecycline, amikacin, extracorporeal membrane oxygenation, and rehabilitation therapy.

Conclusions

The virus was effectively cleared by the combination therapies. The internal genes of the H10N3 virus in this patient were highly homologous to the corresponding genes from the A/Yunnan/2024 virus (GenBank accession numbers, hemagglutinin [HA] [GenBank: PP555669] and PB-2 [GenBank: PP555666]).

Funding

This work was funded by the Fourth People’s Hospital of Nanning - Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) Clinical Treatment Center of Guangxi (Nanning).

Source: Med., https://www.cell.com/med/abstract/S2666-6340(25)00272-7

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History of Mass Transportation: RhB Ge 6/6 Rhaetian Crocodile Electric Locomotive (1921)

 

Von JoachimKohlerBremen - Eigenes Werk, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=50664108

Source: Wikipedia, https://de.wikipedia.org/wiki/Schweizerische_Lokomotiv-_und_Maschinenfabrik

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#Coronavirus Disease Research #References (by AMEDEO, September 20 '25)

 

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