Highly pathogenic avian H5N1 influenza A virus replication in ex vivo cultures of bovine mammary gland and teat tissues

Emerging Microbes & Infections, Год журнала: 2025, Номер unknown

Опубликована: Янв. 9, 2025

Язык: Английский

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Baloxavir improves disease outcomes in mice after intranasal or ocular infection with Influenza A virus H5N1-contaminated cow’s milk

Nature Microbiology, Год журнала: 2025, Номер unknown

Опубликована: Март 17, 2025

Язык: Английский

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Zoonotic Disease Threats: Are We Prepared?

Zoonotic Diseases, Год журнала: 2025, Номер 5(1), С. 1 - 1

Опубликована: Янв. 1, 2025

The coronavirus disease 2019 (COVID-19) pandemic caused great damage not only in terms of morbidity and mortality, but also intense social, economic, institutional political disruptions, costs that upended challenged assumptions about our preparedness to deal with such global infectious threats [...]

Язык: Английский

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Viroporins: discovery, methods of study, and mechanisms of host-membrane permeabilization

Quarterly Reviews of Biophysics, Год журнала: 2025, Номер 58

Опубликована: Янв. 1, 2025

Abstract The ‘Viroporin’ family comprises a number of mostly small-sized, integral membrane proteins encoded by animal and plant viruses. Despite their sequence structural diversity, viroporins share common functional trend: capacity to assemble transmembrane channels during the replication cycle virus. Their selectivity spectrum ranges from low-pH-activated, unidirectional proton transporters, size-limited permeating pores allowing passive diffusion metabolites. Through mechanisms not fully understood, expression facilitates virion assembly/release infected cells, subverts cell physiology, contributing cytopathogenicity. Compounds that interact with interfere membrane-permeabilizing activity in vitro , are known inhibit virus production. Moreover, viroporin-defective viruses comprise source live attenuated vaccines prevent infection notorious human livestock pathogens. This review dives into origin evolution viroporin concept, summarizes some methodologies used characterize structure–function relationships these important virulence factors, attempts classify them on biophysical grounds attending ion/solute transport across membranes.

Язык: Английский

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Immunization with a novel RNA replicon vaccine confers long-lasting protection against H5N1 avian influenza virus in 24 bird species

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 16, 2025

Abstract Highly pathogenic avian influenza viruses (HPAIV) of subtype H5N1 (clade 2.3.4.4b) have spread worldwide and caused the death hundreds millions wild birds domestic poultry. Moreover, spill over HPAIV from infected to more than 50 different mammalian species including humans has been recorded. While, licensed vaccines for protection or are not yet available, a few candidate being trialled. Here, we report on experimental vaccination chickens captive using propagation-defective vesicular stomatitis virus (VSV), in which essential envelope glycoprotein (G) protein gene was replaced by modified hemagglutinin derived clade 2.3.4.4b isolated 2022 animal park Bern, Switzerland. VSVΔG(H5 mb ) produced helper cells providing VSV G trans . Specific pathogen-free (SPF) that were immunized twice via intramuscular route with adjuvant-free replicon particles induced high levels virus-neutralizing serum antibodies fully protected against lethal infection 2.3.4.4b). Notably, animals did shed challenge respiratory gastrointestinal tract, suggesting herd immunity can be achieved. The same vaccine used immunize total 317 at Bern Animal Park Zoo Basel, representing 24 species. No vaccine-associated side effects observed. Birds without previous contact H5Nx very H5-specific neutralizing antibody titers following second immunization, while showing prior vaccination, already developed neutralising after single immunization. One year most still showed significant titers, indicating is able induce long-lasting protective immune response. Our results indicate an extraordinary safe highly efficacious stop replication various

Язык: Английский

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journey of the avian influenza virus H5N1 through 30 years of evolutionary events, geographical locations, and animal species

International Journal of Health Sciences, Год журнала: 2025, Номер 9(1), С. 89 - 108

Опубликована: Янв. 22, 2025

Influenza viruses have caused outbreaks and pandemics throughout human history until Covid-19 been considered the group of with largest potential for pandemics. Avian influenza cause zoonotic diseases, including birds, mammals, humans. This review focuses on H5N1 because it is highly pathogenic generated most common clades among current ones (e.g. 2.3.4.4). Since first goose that was infected in Guangdong, China by A/Goose/Guangdong/1/96 (H5N1) 1996, has undergone many events reassortment other accumulated amino acid substitutions 10 proteins are encoded genome. The will follow through examples such evolutionary permitted virus to spread across world, as well animal species. Hallmark mutations permit or prevent selective binding receptors bird mammal host cells be identified. journey NorthAtlantic fly way from Europe North South America, culminating reported death United States explained. concludes state vaccines anti-virals an assessment author situation.

Язык: Английский

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Pandemic risk stemming from the bovine H5N1 outbreak: an account of the knowns and unknowns

Journal of Virology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 27, 2025

ABSTRACT H5N1 subtype influenza A viruses represent a long-standing pandemic concern. Owing to their global occurrence in poultry, humans are routinely exposed these viruses, and hundreds of human cases have been documented worldwide since 2003. The relevant viral lineages not static, however, recently undergone massive expansion host range geographic distribution. Within this expansion, the introduction into dairy cattle United States has spawned novel animal-human interface. In response, public health agencies sought evaluate risk an stemming from bovine outbreak. These assessments draw on evidence field laboratory score series recognized factors. As such, utility hinges fundamental understanding processes that drive emergence availability data. Advancing gathering data prior during outbreak primary missions NIAID Centers Excellence for Influenza Research Response (CEIRR) Network. To further goals highlight need invigorated response across US agencies, here, we review gaps identify constraints efforts close gaps.

Язык: Английский

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Identification of Amino Acid Residues Responsible for Differential Replication and Pathogenicity of Avian Influenza Virus H5N1 Isolated from Human and Cattle in Texas, US

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 2, 2025

Abstract Highly pathogenic avian influenza viruses (HPAIV) pose a serious public health concern. In March 2024, first-time outbreak of HPAIV H5N1 in dairy cattle herds was reported the United States (US). Since then, virus has continued to spread and spilt over into humans. We recently showed that first human isolate US Texas (HPhTX) from worker an affected farm enhanced replication kinetics pathogenicity mice compared closely related bovine (HPbTX). However, molecular determinants differential have not yet been identified. Herein, we show HPhTX polymerase activity, with HPbTX, cells basic 2 (PB2) protein is main factor responsible for this difference. Through single combined site-directed mutagenesis swapping three amino acids different between found PB2 mutation E627K major contributor activity HPhTX. E362G substitution polymerase, although lesser extent than E627K. Moreover, M631L activity. Rescue loss-of-function recombinant (rHPhTX) containing mutations at residues 627 362, alone or combination, revealed contribution K627E morbidity, mortality, viral as rHPhTX wild-type (WT), significantly reduced levels comparable rHPbTX WT. These findings indicate origin isolated case post-transmission acid changes increase mice.

Язык: Английский

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An intranasal adjuvanted, recombinant influenza A/H5 vaccine candidate induces broad priming against diverse influenza A/H5N1 virus clades in a phase I randomized trial in healthy adults

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 5, 2025

We conducted a randomized, controlled phase I trial (NCT05397119) of novel adjuvanted recombinant influenza A/H5 (A/Indonesia/05/2005, clade 2.1) hemagglutinin vaccine, administered intranasally in two doses 28 days apart at three antigen levels. Control groups received unadjuvanted H5 or formulation buffer placebo. Six months later, participants heterologous inactivated A/H5N1 (A/Vietnam/1203/2004, 1) vaccine intramuscularly. All vaccines were safe and well tolerated. After the primary intranasal series, serum hemagglutination inhibition microneutralization responses minimal. Increases mucosal IgG/IgA, surface plasmon resonance antibody binding, memory B cell CD4 T activity, antibody-dependent cell-mediated cytotoxicity observed only recipients primed with vaccine. Following H5N1 boost, robust across all immune assays, as against diverse clades (including currently circulating 2.3.4.4b), occurred recipients, demonstrating successful priming broad responses. *Meagan E. Deming Franklin R. Toapanta contributed equally.

Язык: Английский

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Digitally Immune-Optimised Next-Generation Influenza H5Nx Vaccination Provides Protection with Broad Cross-Clade Neutralisation Against Global Threats

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 21, 2025

A panzootic of H5Nx avian influenza viruses has severely affected poultry and wild bird populations, resulting in multiple mammalian spillovers, including mild to fatal human infections caused by antigenically distinct diverse virus clades. The unpredictable nature spillover events drifted hinders our ability effectively respond the heightened risk human-to-human transmission. Stockpiled strain-specific H5 whole virus-based vaccines provide limited breadth reduced efficacy. To address this problem, we computationally designed vaccine antigens that induce broad protective immune responses. Ferrets immunised with DVX-panH5Nx mRNA candidate generated potent responses across a wide spectrum A/H5 Furthermore, ferrets DVX-pan-H5Nx demonstrated superior protection when compared an industry standard inactivated derived from A/Astrakhan/3212/2020 (H5N8), against lethal heterologous challenge.

Язык: Английский

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