Membrane-anchored #influenza #neuraminidase vaccine drives #human-like broadly protective B cell responses

 

Abstract

Influenza neuraminidase (NA) is a promising target for universal flu vaccines, yet eliciting potent B-cell responses against its conserved epitopes remains challenging. Here, we developed a membrane-anchored, folding-domain-free NA (mNA) that elicited superior head-specific germinal center B cell and antibody responses compared to soluble tetrameric NA. In non-human primates, mNA immunization induced cross-reactive memory B cell (MBC) responses, expanding clones with the conserved DR motif in HCDR3, a hallmark of human broadly reactive NA antibodies. These MBCs conferred cross-inhibitory activity against diverse NA variants and in vivo cross-protection. Cryo-EM analysis revealed that the 554-C2 clone targets the conserved enzymatic pocket via the DR motif, while the 554-C1 clone recognizes previously uncharacterized epitopes at the interface between two adjacent N2 monomers, effectively reducing plaque formation by contemporary H3N2 strains. Our findings highlight the immunological advantages of membrane-anchoring, providing a robust strategy for designing next-generation vaccines against influenza and other pathogens.

Competing Interest Statement

Westlake University has filed for patent protection for mNA used as an influenza vaccine.

Funder Information Declared

State Key Laboratory of Gene Expression, SKLGE-ZX-2025007

Zhejiang Provincial Key Laboratory Construction Project, 2024ZY01026, 2024E10060, 2024E10052

Natural Science Foundation of Zhejiang province, LR26H190001

National Natural Science Foundation of China, 82471855, 825B2062, 82330054, 82502209, 32471303

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.05.13.724804v1

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A Panel of #Human Monoclonal #Antibodies for Tracking the #Antigenic #Evolution of #Influenza #H5N1 Clade 2.3.4.4b

 

Abstract

The ongoing panzootic of clade 2.3.4.4b H5N1 influenza has resulted in widespread infection of birds, mammals, and livestock, underscoring the need for tools to interpret its real-time evolution. Here, we describe the isolation and characterization of a panel of 19 human monoclonal antibodies that potently neutralize current isolates. Competition immunoassays and cryo-electron microscopy analyses revealed their collective near-complete epitope coverage of the H5-hemagglutinin surface. Neutralization profiling across multiple historical and contemporary H5 viruses defined their epitope-specific patterns of virus neutralization. One cluster of antibodies potently neutralized only clade 2.3.4.4b viruses, while many others exhibited broadly neutralizing activity against diverse H5N1 clades. Application of this structurally calibrated antibody panel to recent North American human isolates revealed genotype-specific antigenic divergence between lineages that have spread among cattle (B3.13) and poultry (D1.1). Together, the findings of this study establish a structurally grounded antibody reference panel spanning major vulnerable sites of H5 hemagglutinin and provide a toolbox for interpreting emergent mutations, monitoring ongoing antigenic drift, and anticipating the evolutionary trajectory of circulating H5N1 influenza viruses.

Competing Interest Statement

H.H., M.W., S.C., J.Y., Y.H., Y.G., and D.D.H. are inventors on the provisional patent application filed by Regeneron for several H5N1 neutralizing antibodies described herein. D.D.H. is a co-founder of TaiMed Biologics and RenBio, consultant to Brii Biosciences, and board director for Vicarious Surgical.

Funder Information Declared

Gates Foundation, INV019355

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.05.14.725215v1

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#Reassortant High Pathogenicity Avian #Influenza #H5N1 Viruses During the Reemergence in #Uruguay Suggest Increasing #Genetic Diversity in South #America

 

Abstract

Highly pathogenic avian influenza (HPAI) H5N1 viruses of the goose/Guangdong (Gs/GD) lineage have driven a global panzootic since 2020, with clade 2.3.4.4b establishing sustained transmission in wild birds. In South America, early outbreaks were largely associated with the North American-derived B3.2 genotype, which showed limited diversification after its introduction. Here, we report the genomic characterization of eight H5N1 viruses detected in Uruguay during the reemergence of avian influenza in February–March 2026. Complete genomes were obtained from wild birds exhibiting neurological signs, predominantly Coscoroba coscoroba. All viruses belong to clade 2.3.4.4b but exhibit a reassortant genomic constellation distinct from B3.2. The HA, NA, and MP segments retain the Eurasian backbone, whereas internal genes derive from both South American and North American low-pathogenicity avian influenza lineages. PB2 variation distinguishes two closely related viral groups differing in PB2 origin, whereas the remaining genomic segments retain a shared background. Sequence variation in the neuraminidase gene reduced the sensitivity of a widely used N1-specific RT-qPCR assay, highlighting limitations of existing diagnostic tools during viral evolution. These findings confirm the presence of reassortant H5N1 viruses in Uruguay and, together with recent reports from Argentina and Brazil, support an emerging pattern of genomic diversification in southern South America.

Source: 

Link: https://www.mdpi.com/1999-4915/18/5/558

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#Diagnostic and #clinical #challenges of #hantavirus-associated acute #kidney injury

 

Abstract

Introduction: 

Hantavirus infection is an uncommon zoonosis in Europe but remains an important cause of acute kidney injury, particularly in patients with environmental exposure to rodents. Renal involvement is the hallmark of the disease, although pulmonary manifestations may coexist and mimic immune-mediated pulmonary–renal syndromes, leading to diagnostic challenges in internal medicine.

Case description: 

A 46-year-old previously healthy man living in a rural area was admitted for acute febrile illness with asthenia and myalgia. Initial investigations revealed severe thrombocytopenia and acute kidney injury with proteinuria and microscopic haematuria. A computed tomography scan of the chest and abdomen showed bilateral pulmonary abnormalities, consistent with an acute pulmonary–renal syndrome. Extensive immunological and infectious investigations excluded autoimmune disease and alternative infectious causes. Hantavirus infection was confirmed by positive IgM and IgG serology, with molecular identification of Puumala virus. Renal biopsy demonstrated moderate acute tubular necrosis with minimal interstitial inflammation and preserved glomeruli. The patient was treated with supportive care only, resulting in rapid clinical improvement and complete recovery of renal function.

Conclusion: 

Hantavirus infection should be considered in patients presenting with acute pulmonary–renal syndrome, thrombocytopenia, and compatible epidemiological exposure. Early diagnosis allows appropriate supportive management, avoids unnecessary immunosuppressive therapy, and is associated with an excellent renal prognosis in Puumala virus infection.

Source: 

Link: https://www.ejcrim.com/index.php/EJCRIM/article/view/6159

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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

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#Ensitrelvir for #Covid19 Postexposure #Prophylaxis in #Household Contacts

 

Abstract

Background

Ensitrelvir, an oral inhibitor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3C-like protease, is approved in Japan for the treatment of mild-to-moderate coronavirus disease 2019 (Covid-19). Previously, no antiviral agents were approved for postexposure prophylaxis in household contacts of patients with Covid-19.

Methods

In this double-blind, randomized, placebo-controlled trial, we randomly assigned persons who were SARS-CoV-2–negative on local diagnostic testing but were household contacts of a patient with Covid-19 (the index patient) to receive either ensitrelvir (375 mg on day 1 and 125 mg daily on days 2 through 5) or placebo within 72 hours after symptom onset in the index patient. The primary end point was Covid-19 (defined by a central laboratory–confirmed positive reverse-transcriptase–polymerase-chain-reaction assay and the presence of ≥1 of 14 prespecified Covid-19 symptoms lasting ≥48 hours) by day 10 in a household contact in the modified intention-to-treat population (all the participants who underwent randomization, had a central laboratory–confirmed negative RT-PCR test for SARS-CoV-2 at baseline, and received at least one dose of the trial drug or placebo).

Results

The modified intention-to-treat population included 1030 participants in the ensitrelvir group and 1011 in the placebo group. The mean age of the participants was 42.4 years; 71.1% had undergone randomization within 48 hours after symptom onset in the index patient, and 37.0% had at least one risk factor for severe Covid-19. The incidence of Covid-19 was lower in the ensitrelvir group than in the placebo group (2.9% vs. 9.0%; risk ratio, 0.33; 95% confidence interval [CI], 0.22 to 0.49; P<0.001). The incidence of adverse events during the trial was similar in the two groups (15.1% in the ensitrelvir group and 15.5% in the placebo group), as was the incidence of serious adverse events (0.2% in each group). No Covid-19–related hospitalizations or deaths were reported.

Conclusions

Ensitrelvir administered to household contacts of a patient with Covid-19 within 72 hours after symptom onset in the index patient was effective in preventing Covid-19 in the contacts. (Funded by Shionogi; SCORPIO-PEP Japan Registry for Clinical Trials number, jRCT2031230124; ClinicalTrials.gov number, NCT05897541.)

Source: 

Link: https://www.nejm.org/doi/full/10.1056/NEJMoa2509306?query=TOC

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#Outbreak of #H9N2 avian #influenza viruses in lesser #rhea in #Peru, June-July 2025

 

Abstract

Avian influenza viruses (AIVs) are endemic in the Americas and responsible for outbreaks in both domestic and wild birds that occasionally spill over into humans. We report the first known outbreak of AIV H9N2 in lesser rhea (Rhea pennata), also known as Darwin’s rhea, in the region of Puno-Peru. The animals in this study lived in an isolated conservation center located in remote highlands above 4,000 m.a.s.l. Between June and July 2025, a total of 46/92 animals were recorded sick, with symptoms including greenish diarrhea (100%), hyporexia (24%), dyspnea (76%), nasal discharge (42%), drowsiness (18%) and isolation from the flock (73%), and 94% later died. Gross pathology exams revealed septicemia characterized by severe hepatitis, pneumonia, tracheitis, enteritis, and encephalitis. Swab and necropsy samples tested positive for Influenza A by PCR and were later identified as H9N2 through whole genome sequencing. We generated complete H9N2 genomes for two individuals. No additional pathogens were found. Phylogenetic analysis across all eight segments revealed that the viruses were low pathogenicity H9N2 AIV strains of North American origin, which indicated this outbreak was a new introduction of the virus into South America. We also performed a comparative mutational analysis and identified multiple mutations previously associated with mammalian host adaptation, increased virulence, increased pathogenicity, and increased virus binding to α2-6 receptors, which may explain the high mortality rates observed despite the supposedly low pathogenicity of the strain. We also identified novel mutations specific to rhea viruses that will need to be experimentally validated. This is the first report of a natural H9N2 systemic infection in an avian host, highlighting a need for increased surveillance efforts for zoonotic influenza viruses with pandemic potential.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.05.08.723762v1

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Emerging and re-emerging vector-borne and other #zoonotic #RNA #viruses: #pathogenesis, #climate-driven dynamics, and strategies for global control

 

Abstract

Vector-borne and other zoonotic RNA viruses provide a significant and growing threat to global health, especially in areas where climate change, urbanization, and population growth facilitate the proliferation of arthropod vectors. This review offers an extensive examination of the biology, epidemiology, and pathogenesis of numerous important viruses, including dengue, Zika, chikungunya, yellow fever, Japanese encephalitis, Crimean–Congo hemorrhagic fever, Nipah, Ebola, and hantaviruses. We underscore how environmental and social factors, particularly increasing temperatures, modified precipitation patterns, and accelerated urbanization, transform vector habitats and spillover dynamics. The article further analyzes host–virus and virus–vector interactions, highlighting mechanisms of immune evasion, neurotropism, and vascular disease. Computational and machine learning models are examined as novel instruments for forecasting outbreaks and developing early warning systems. Finally, a summary of present and prospective control options is provided, covering integrated vector management, Wolbachia-based biological control, vaccinations, and antiviral immunotherapies.

Source: 

Link: https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2026.1755594/full

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Pre-existing systemic and #nasal #antibodies against avian #H5 #influenza A viruses vary according to #childhood imprinting

 

Abstract

Avian influenza A viruses (IAV) pose a constant pandemic threat, with the recent 2.3.4.4b clade of the H5 subtype causing high pathogenicity and spreading across animal species and geographic locations. Understanding human pre-existing immunity to avian H5 IAV can inform on population susceptibility, a critical aspect of pandemic preparedness. To that end, we analysed the IAV HA-specific antibodies across individuals born between 1928-1999 with different early life exposures to IAV subtypes. Individuals born prior to 1957 had the highest pre-existing serum antibodies to group 1 HA antigens, including the 2.3.4.4b H5 and a group 1 HA stem antigen. These birth-year-specific patterns were not reflected in the limited pre-existing serum neutralising antibodies detectable against a 2.3.4.4b H5 IAV or in H5-specific memory B cell populations. They were however evident in pre-existing nasal IgG and IgA titres to H5, which were greater in individuals born prior to 1957. Our findings demonstrate that the immunological biases afforded by early life exposure extend to antibodies detected in the nasal mucosa, the site of IAV replication.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.05.08.723737v1

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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

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The #Coinfection of #Bartonella spp. and #Hantavirus in Wild #Rodent and #Shrew Species in Eastern #China

 

Abstract

Background:

Bartonella spp. are Gram-negative bacteria that cause diseases including endocarditis, lymphadenopathy, and neuroretinitis. Hantavirus (HV), belonging to the family Hantaviridae, induces illnesses such as hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome. Both pathogens exhibit host specificity—defined as a preference or restriction to specific host species or ranges. Rodents and shrews are primary hosts for these pathogens, and their high coinfection rates often indicate elevated risk of human exposure. To our knowledge, however, data on Bartonella spp.–HV coinfection in rodents and shrews from Eastern China remain limited.

Materials and Methods:

Between 2020 and 2023, rodents (n = 311) and shrews (n = 16) were investigated for coinfection with Bartonella spp. and HV in Qingdao, eastern China. Nested Polymerase Chain Reaction (PCR) was used for the detection of RNA-dependent RNA polymerase (RdRp) gene of HV and the Internal Transcribed Spacer, citrate synthase (gltA) and RNA polymerase beta subunit (rpoB) genes of Bartonella spp.

Results:

The overall infection rates of Bartonella spp., HV, and coinfection were 21.4%, 6.7%, and 4.0%, respectively. The highest rates were observed in Apodemus agrarius (53.8%, 21.3%, and 15.0%). Coinfection rates differed significantly by species (p < 0.05), with A. agrarius exhibiting the highest rate (15.0%). Notably, the coinfection rate was significantly higher in male (28.9%) than female A. agrarius (7.1%) (p < 0.05).

Conclusions:

This study confirms the coinfection of Bartonella spp. and HV in rodents in the eastern region of China. Enhanced monitoring of rodent and shrew densities, as well as their carried pathogens, is essential. Additionally, timely screening, diagnosis, and treatment should be conducted for high-risk populations in the region to reduce the incidence of related zoonoses.

Source: 

Link: https://journals.sagepub.com/doi/10.1177/15303667261448824

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#Genomic Analysis of #SinNombre Virus #Sequences, Northwestern #USA, 2023

 

Abstract

We report Sin Nombre virus (SNV) genome sequences in the northwestern United States, including SNV sequences recovered from montane voles. Analysis of samples collected from 189 individual rodents revealed high SNV prevalence in the region and evidence of virus reassortment or coinfection, highlighting ongoing virus diversification in rodents.

Source: 

Link: https://pubmed.ncbi.nlm.nih.gov/42116630/

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Sequencing of #Betacoronavirus erinacei from faeces of pet #hedgehogs demonstrates a continuity of #MERS-CoV like viruses in #European and Eurasian hedgehog species

 

Abstract

Hedgehogs have been recently identified as carriers of Betacoronavirus erinacei (also known as Erinaceus coronavirus, EriCoV) a virus closely related to B. cameli responsible for human Middle East Respiratory Syndrome (MERS), raising questions about the risk of hedgehog-to-human transmission and suggesting the need for coronavirus (CoV) surveillance in hedgehogs. This study investigated the presence of CoVs in fecal samples of hedgehogs kept as pets in Italy in 2021–2022. A pan-CoV nested RT-PCR targeting the RdRp gene was used for screening and positive samples were sequenced and phylogenetically analyzed. Two (6.2%) out of 30 hedgehogs analyzed were positive for B. erinacei represented by 2/3 (66.7%) long eared hedgehog (Hemiechinus auritus) while all the 27 tested African pygmy hedgehog (Atelerix albiventris) were negative. Whole genome sequence obtained from one B. erinacei-positive sample showed closest homology (85.7%) with B. erinacei previously detected in Erinaceus sp. from Eastern Russia. Phylogeny showed that the virus of this study formed a separate clade in the cluster with other B. erinacei identified in Europe and European Russia and did not cluster with other B. erinacei identified in China in Amur hedgehog (E. amurensis). No recombination events were observed. Analysis of the Spike protein revealed the presence of six out of the 11 key receptor binding residues, including two out of the three critical residues recently identified for the binding of Erinaceus europaeus receptor APN and B. erinacei. Results of this study suggest the presence of a long-eared hedgehog-specific strain of B. erinacei. Overall results support the circulation of coronaviruses along a phylogenetic continuum among different species of hedgehogs and geographic locations, suggesting the need for further CoV surveillance in both domestic and wild animals. There is also a need for studies on the affinity of EriCoV with the H. auritus APN specific receptor to confirm its involvement in the viral entry process.

Source: 

Link: https://www.sciencedirect.com/science/article/pii/S2352771426000960?via%3Dihub

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Cross-reactive #human #antibody responses to #H5N1 #influenza virus #neuraminidase are shaped by immune history

 

Abstract

H5N1 highly pathogenic avian influenza viruses have spread globally and pose a pandemic risk. Prior studies suggest that early life exposures to group 1 influenza viruses (H1N1 and H2N2) prime antibodies that cross-react to the hemagglutinin of H5N1, which is also a group 1 virus. However, less is known about how immune history affects antibody responses against the H5N1 neuraminidase (NA). We measured NA inhibition antibodies against multiple H5N1 viruses using sera from 155 individuals born between 1927 and 2016. Individuals likely primed in childhood with H1N1 viruses possessed higher levels of antibodies that cross-react with the NA of H5N1 viruses compared to those primed with H2N2 or H3N2 viruses. While young children rarely possessed cross-reactive N1 antibodies, childhood infections with contemporary H1N1, but not H3N2, viruses elicited them. We also measured antibodies against an H5N5 virus (A6 genotype) that recently caused a fatal infection in the United States. Consistent with the lack of circulation of N5 viruses in humans, we found low levels of antibodies against the N5 NA. Our data suggest that immune history greatly impacts the generation of cross-reactive NA antibodies, and that reassortment with other NAs may increase the risk of H5 infection of humans.

Source: 

Link: https://www.nature.com/articles/s41467-026-72941-4

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The Decline in #Influenza #Antibody Titers and Modifiers of #Vaccine #Immunity from over Ten Years of Serological Data

 

Abstract

Annual influenza vaccination is the cornerstone for seasonal protection, yet antibody responses are highly variable across individuals and over time. To systematically assess the determinants of this heterogeneity, we compiled 20,449 hemagglutination inhibition and neutralization titers from 4,540 participants enrolled in 14 new vaccine studies we conducted and 50 prior studies that collectively span 2010-2023. Seasonal effects dominated, with pre- and post-vaccination titers declining steadily from 2017 onwards, outweighing the influence of age, sex, or repeated vaccination. Titers to B Yamagata remained steady throughout all years examined, suggesting unique durability and offering a reason for lineage extinction. Vaccine timing emerged as a strong and previously underappreciated determinant of immunity, with individuals vaccinated later in the season exhibiting larger post-vaccination titers. Not being vaccinated or receiving the live-attenuated FluMist vaccine in one year significantly enhanced the response to inactivated vaccines in 45% or 68% of cohorts, respectively, whereas antigen dose and adjuvants had modest impact. These findings identify vaccine timing and seasonal context as underrecognized drivers of immunogenicity and provide actionable insights for optimizing influenza vaccination strategies.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This research was supported by the the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) under the Computational Models of Influenza Immunity (U01 AI187062), LJI & Kyowa Kirin, Inc. (KKNA - Kyowa Kirin North America), and the Bodman family (TE).

Source: 

Link: https://www.medrxiv.org/content/10.64898/2026.01.07.25342310v2

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Computational Structural Analysis Predicts #Host-Range Promiscuity and #Antiviral #Resistance in North #American #H5N1 Lineages

 

Abstract

Influenza A virus has been circulating in birds in Eurasia for more than 146 years, but human infection has been sporadic. H5N1 (clade 2.3.4.4b) has recently infected hundreds of species of wild and domestic birds and mammals in North America. Infections include 71 people in the United States. There have been 2 human fatalities (United States and Mexico). We have integrated time-series analysis, molecular phylogenetics, and structural biology to understand how H5N1 is circulating in North America and adapting to new hosts. Our time-series analysis reveals that the circulation of H5N1 follows a distinct seasonal pattern, with cases in the United States increasing November to April. We also document an increase in the number of cases reported since 2021. We show that H5N1 spreads in North America as 2 distinct lineages. These viral lineages have achieved a vast host range by efficiently binding the viral surface protein hemagglutinin to both mammalian and avian cell surface receptors. This novel host-range promiscuity is concomitant with the strengthening of the viral polymerase basic 2 protein binding for mammalian and avian immune proteins. Once bound, the immune proteins have diminished ability to fight the virus, thus allowing for efficient replication. Our analyses predict that while most antivirals remain effective, a fatal human isolate showed reduced binding to multiple drugs from different classes. The H5N1 virus is causing an animal pandemic through promiscuity of host range and strengthening ability to evade the innate immune systems of both mammalian and avian cells.

Source: 

Link: https://spj.science.org/doi/10.34133/csbj.0066

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Identification and #genetic characterization of a distinct #genotype of #Puumala #orthohantavirus in #Hebei Province, #China

 

Abstract

Orthohantavirus infections pose a significant threat to human health, while numerous orthohantaviruses have been identified, suspected viral infections remain undiagnosed in the world, which highlights the need for further identification and characterization of viruses circulating in humans and host animals. In this study, viral metagenomics was utilized to investigate orthohantaviruses present in tissue samples collected from rodents trapped at the Bashang Grassland of Hebei Province, China. A total of 145 wild rodents belonging to six species were captured in the study area, and 725 tissue samples (lung, liver, kidney, spleen, gut) were collected in 2024. A Puumala orthohantavirus (PUUV), named Guyuan strain, was identified in Myodes rufocanus, with a positive rate of 0.69%. The complete genomic sequences of the L, M, and S segments were obtained and confirmed by Sanger sequencing. Phylogenetic analysis of these genomic sequences with those of other orthohantavirus species showed that the L, M, and S segments clustered with PUUV genomic sequences, while sharing a nucleotide sequence similarity of 81.2%, 80.2%, and 84.3% with previously characterized reference viral strains Kitahiyama128L, Tobetsu_04, and Baltic/205 Cg, respectively. Amino acid homology analysis demonstrated that the sequences exhibited the highest identity to PUUV Hokkaido strain at a level of 95.4%, 94.6%, and 97.0% respectively. Viral particles were observed in lung and kidney tissues using transmission electron microscopy, and viral protein antigen was detected in viral RNA-positive lung, liver, and kidney tissues through immunofluorescence assay with antibodies against the PUUV nucleocapsid protein, thereby confirming the virus’s multiorgan tropism. The results demonstrated that a distinct genotype of PUUV was circulating in rodents in the study areas, which may have implications for zoonotic transmission surveillance and public health management in Hebei Province.

Source: 

Link: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014250

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When Rare #Zoonoses #Travel: #Andes virus, #Hantavirus Cardiopulmonary Syndrome, and the #Preparedness Gap

 

Abstract

The perspective discusses how the suspected Andes virus (ANDV) associated hantavirus cluster on the expedition cruise ship MV Hondius illustrates a critical preparedness gap in managing rare zoonotic infections in mobile, closed, and medically constrained settings. Focusing on the reported multi-country cluster involving severe hantavirus cardiopulmonary syndrome, deaths, and international passenger dispersal, it highlights the associated diagnostic, clinical, and epidemiological challenges. The perspective also explains why ANDV is distinct among hantaviruses, including its documented potential for limited person-to-person transmission during close and prolonged contact, with insights into the virology and pathogenesis of ANDV. Additionally, it highlights ecological exposure hazards in Patagonia, rodent reservoirs, clinical progression, the necessity for laboratory confirmation, candidate severity biomarkers such as IL-6 and intestinal fatty acid-binding protein, and the lack of specific antiviral therapy. Furthermore, it discusses risk factors, including European ethnicity and host genetic susceptibility linked to αVβ3 integrin variation. Overall, this perspective argues that expedition travel, maritime medicine, One Health surveillance and outbreak preparedness must be better integrated in order to detect, investigate and manage rare but high-consequence zoonotic infections before they escalate into international public health events.

Link: https://pubmed.ncbi.nlm.nih.gov/42107872/

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A single PA-X #mutation in #bovine-origin #H5N1 #influenza virus reduces #pathogenicity in mice

 

Abstract

Dairy cows have emerged as a reservoir for human infection with highly pathogenic avian influenza (HPAI) H5N1. At the bovine-human interface, H5N1 strains may acquire adaptive mutations that influence their zoonotic potential. Sequence analysis identified a K142E substitution (bovine to human) in the PA and PA-X proteins, with the potential to affect both polymerase activity and host shutoff. Here, we used a loss-of-function approach to investigate how the bovine substitution (E142K) in PA/PA-X impacts viral replication, host shutoff activity, and pathogenicity in the human H5N1 background. Viral growth kinetics demonstrated that the virus containing the E142K substitution is attenuated, with reduced replication compared to wild-type (WT) virus. Consistently, PA-X-mediated host shutoff activity was reduced, resulting in increased induction of interferon (IFN) responses relative to WT. In vivo, mice infected with the E142K mutant virus survived, whereas infection with the WT virus was uniformly lethal. Despite comparable viral titers and inflammation score in mouse lungs, cytokine and chemokine profiling revealed distinct immune responses, with reduced CCL2 and increased CCL5 and IFN-γ in mice infected with the E142K mutant virus compared to mice infected with the WT virus. These findings indicate that increased virulence of the human-adapted strain is driven by a PA-X mutation that modulates inflammatory responses, producing distinct immune signatures linked to host survival or viral lethality rather than changes in polymerase activity by PA. Collectively, these results highlight PA-X as a key determinant of pathogenicity of H5N1 and a potential target for the rational design of antiviral strategies.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.05.09.724031v1

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#Detection and #isolation of #H5N1 clade 2.3.4.4b #influenza virus from #ticks recovered from a naturally infected slender-billed #gull

 

Abstract

Laridae birds, such as gulls, are known reservoirs of H13 and H16 low pathogenicity avian influenza virus (LPAIV) subtypes. However, during the recent outbreaks linked to the reemergence of high pathogenicity avian influenza virus (HPAIV) H5N1 clade 2.3.4.4b of the Goose/Guangdong lineage, European populations of Laridae birds suffered significant losses. HPAI cases were reported not only along the coastlines but also inland areas, particularly in France and Central Europe. During a diagnostic investigation of a group of Laridae birds, part of a HPAIV outbreak reported in the South of France in 2023, larval stages of Ornithodoros maritimus, a nidicolous soft tick parasitizing seabirds, were recovered from a slender-billed gull (Chroicocephalus genei). Affected birds exhibited gross and histopathological lesions consistent with systemic HPAIV infection. Immunohistochemistry revealed marked neurotropism, oculotropism and multicentric epitheliotropism. Viral isolation and sequencing analysis confirmed the presence of HPAIV H5N1 clade 2.3.4.4b in both the gull and ectoparasites, showing from 99.64% to 100% nucleotide identity across five of eight RNA segments. While additional research is needed to properly assess the vector competence of O. maritimus for HPAIV, ticks may represent an interesting non-invasive surveillance tool for these viruses. This is the first time a HPAIV has been successfully isolated from tick larvae. These findings represent a first step toward understanding the potential role played by ticks in the spread of avian influenza viruses within marine bird colonies and among other ecosystems, considering the occurrence of specific behavioral traits, such as kleptoparasitim and the position of gulls at the interface between wild and domestic species.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Agence Nationale de la Recherche, https://ror.org/00rbzpz17

INRAe Animal Health Department

Source: 

Link: https://www.biorxiv.org/content/10.1101/2025.11.28.689408v2

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