#ah5n1 — Public Fediverse posts

#Influenza A(#H5N1) shedding in #air corresponds to #transmissibility in #mammals

Source: Nature Microbiology, https://www.nature.com/articles/s41564-024-01885-6

Abstract
An increase in spillover events of highly pathogenic avian influenza A(H5N1) viruses to mammals suggests selection of viruses that transmit well in mammals. Here we use air-sampling devices to continuously sample infectious influenza viruses expelled by experimentally infected ferrets. The resulting quantitative virus shedding kinetics data resembled ferret-to-ferret transmission studies and indicated that the absence of transmission observed for earlier A(H5N1) viruses was due to a lack of infectious virus shedding in the air, rather than the absence of necessary mammalian adaptation mutations. Whereas infectious human A(H1N1pdm) virus was efficiently shed in the air, infectious 2005 zoonotic and 2024 bovine A(H5N1) viruses were not detected in the air. By contrast, shedding of infectious virus was observed for 1 out of 4 ferrets infected with a 2022 European polecat A(H5N1) virus and a 2024 A(H5N1) virus isolated from a dairy farm worker.

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#aH5n1 #abstract #animalModels #avianInfluenza #AVIANINFLUENZA #birdFlu #dairyCow #h5n1 #health #news #pathogensAirborneTransmission #research

Polygenic #Determinants of #H5N1 #Adaptation to Bovine Cells

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.11.29.626120v1

Abstract
H5N1 avian influenza virus (lineage 2.3.4.4b, B3.13 genotype) has caused, unexpectedly, a large outbreak in dairy cattle in North America. It is critical to ascertain how this virus has specifically adapted to bovine cells and the molecular determinants of this process. Here, we focused on the contribution of the viral internal genomic segments of H5N1 B3.13 to bovine cells adaptation. We generated 45 reassortant viruses harbouring the haemagglutinin and neuraminidase from A/Puerto Rico/8/1934 and internal gene constellations from several influenza A viruses (IAV) or carrying segment swaps between distinct H5N1 strains. The recombinant B3.13 viruses displayed faster replication kinetics in bovine cells compared to other IAV. Importantly, multiple genomic segments of B3.13 viruses contribute to their faster replicative fitness. Further, recombinants with the B3.13 internal genes were less susceptible than ancestral 2.3.4.4b strain to the bovine IFN response. However, bovine (and human) MX1, a key restriction factor for avian IAV, restricted both ancestral 2.3.4.4b and B3.13 recombinant viruses. Interestingly, the latter escape restriction from human BTN3A3. Finally, recombinant B3.13 was virulent in mice unlike the ancestor 2.3.4.4b recombinant virus. Our results highlight the polygenic nature of influenza host range as multiple internal genes of B3.13 contribute to bovine adaptation.

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#aH5n1 #abstract #animalModels #avianInfluenza #AVIANINFLUENZA #birdFlu #dairyCow #h5n1 #health #news #research #viralPathogenesis

Single-dose avian #influenza A(#H5N1) Clade 2.3.4.4b #hemagglutinin-Matrix-M nanoparticle #vaccine induces neutralizing responses in nonhuman #primates

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.11.21.624712v1?rss=1

Abstract
With the recent rise in cases of highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b infection in humans and animals, there is an associated increase in the risk of human-to-human transmission. In this study, we characterize recombinant A(H5N1) A/American Wigeon/South Carolina/22/000345-001/2021 (A/AW/SC/2021) clade 2.3.4.4b vaccine. Purified recombinant A/AW/SC/2021 HA trimers upon formulation with Matrix-M™ adjuvant, saponin-cholesterol-phospholipid icosahedral particles, non-covalently anchored to the vertices of the Matrix-M forming A(H5N1) HA–Matrix-M nanoparticles (H5-MNPs). In naive mice, two intranasal (IN) or intramuscular (IM) doses of A/AW/SC/2021 H5-MNP vaccine induced robust antibody- and cell-mediated immune responses, including neutralizing antibodies against A(H5N1). In non-human primates (NHPs) primed with seasonal influenza vaccine, a single IM or IN dose of the A/AW/SC/2021 H5-MNP vaccine induced geometric mean serum A(H5N1) clade 2.3.4.4b pseudovirus neutralizing titers of 1:1160 and 1:54, respectively; above the generally accepted seroconverting neutralizing titer of 1:40. Immunization with H5-MNP vaccine induced antibody responses against conserved epitopes in the A(H5N1) HA stem, vestigial esterase subdomain, and receptor binding site. This novel A(H5N1) H5-MNP IN and IM vaccine was immunogenic in rodents and NHPs as a potential A(H5N1) pandemic single-dose vaccine.

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#aH5n1 #abstract #animalModels #avianInfluenza #AVIANINFLUENZA #birdFlu #h5n1 #health #news #pandemicPreparedness #research #vaccines

#Chicken ANP32A-independent #replication of highly pathogenic avian #influenza viruses potentially leads to #mammalian #adaptation-related amino acid substitutions in viral #PB2 and #PA proteins

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.01840-24?af=R

ABSTRACT
Acidic nuclear phosphoprotein 32 family member A (ANP32A) is an important host factor that supports the efficient replication of avian influenza viruses (AIVs). To develop an antiviral strategy against Gs/Gd-lineage H5 highly pathogenic avian influenza (HPAI) viruses in chickens, we established chicken ANP32-knockout (chANP32A-KO) DF-1 cells and evaluated their antiviral efficacy through in vitro validation. The replication of all HPAI viruses tested in chANP32A-KO cells was significantly lower compared to that of wild-type DF-1 cells. However, when HPAI strains A/mountain hawk-eagle/Kumamoto/1/2007 (H5N1; MHE) and A/chicken/Aichi/2/2011 (H5N1; H5Aichi) were passed in chANP32A-KO cells, mutant viruses were generated, which exhibited comparable replication levels in both chANP32A-KO and wild-type DF-1 cells. Sequence analysis revealed that mammalian-adaptive amino acid mutations PB2_D256G and PA_T97I were present in the MHE mutant virus, and the PB2_E627K mutation was identified in the H5Aichi mutant virus. These mutations have also been reported to enhance the polymerase activity of AIVs in mammalian cells; however, the minigenome assay in the present study showed that the polymerase activity of mutant viruses in chANP32A-KO cells was not restored to levels comparable to those in wild-type DF-1 cells. These findings suggest that ANP32A-independent viral replication may induce amino acid substitutions associated with mammalian adaptation in AIVs. They also imply that the high efficiency of viral replication mediated by these amino acid mutations may not result from enhanced polymerase activity but rather involve other undefined mechanisms.

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#aH5n1 #abstract #animalModels #avianInfluenza #AVIANINFLUENZA #biology #birdFlu #health #research #science

Enhanced #encephalitic #tropism of #bovine #H5N1 compared to the #Vietnam #H5N1 isolate in #mice

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.11.19.624162v1

Abstract
In recent years, the landscape of highly pathogenic avian influenza (HPAI) virus infections has shifted, as evidenced by an increase in infections among mammals. This includes the recent circulation of H5N1 in dairy cattle herds in the USA and a rise in associated human cases. In this study, we investigated differences in tissue tropism of two HPAI H5N1 strains, the isolate A/Vietnam/1203/2004 (VN1203) isolated from a fatal human case in 2004 and the bovine isolate A/Bovine/Ohio/B24osu-342/2024 (Bov342) isolated in 2024, in C57BL/6J mice. Infection with either HPAI H5N1 isolate was uniformly lethal in mice. However, tissue tropism differed significantly: while VN1203 replication was largely restricted to the respiratory tract, Bov342 successfully replicated in the respiratory tract as well as various regions of the brain. Bov342-challenged animals exhibited clinical signs consistent with central nervous system (CNS) infection, and infectious virus was detected in brain tissue. Correspondingly, cytokine profiles in the brain differed significantly between the isolates. Notably, in addition to abundant evidence of CNS infection in Bov342-challenged mice via immunohistochemistry, sporadic intranuclear and intracytoplasmic immunoreactivity was observed in other tissues in the head, including the choroid plexus, retina, and inner ear. This study demonstrates that while both HPAI H5N1 isolates are uniformly lethal in C57BL/6J mice upon aerosol exposure, significant differences exist in tissue tropism, with Bov342 resulting in respiratory disease as well as increased neurotropism and inflammation in the brain and nasal turbinates compared to VN1203, which predominantly induces respiratory disease.

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#research #abstract #avianInfluenza #aH5n1 #animalModels #neuroinvasion #animalHealth #health #news #birdFlu #h5n1 #AVIANINFLUENZA #dairyCow