Intramammary infection of bovine H5N1 influenza virus in ferrets leads to transmission and mortality in suckling neonates DOI Creative Commons
Pari H. Baker, Mary Pat Moyer, Yongying Bai

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 16, 2024

Abstract The spread of H5N1 clade 2.3.4.4b in dairy herds raises concerns about zoonotic transmission due to the high viral load milk, a key point contact between livestock and humans. exhibits tropism for mammary gland, with milk from infected cows containing levels RNA infectious virus. virus’s ability infect gland suggests potential risks offspring through breastfeeding. Here, we show that infection bovine influenza lactating ferrets transmits virus disease suckling kits. Viral titers significantly increased over time remained tissue. Suckling kits had oral nasal cavity, as well feces. However, detection dam cavities was delayed, only minimal present cavity. Lung were low dams but sampled kit. Additionally, detected expression receptor, α2,3 sialic acid, tissue both These data demonstrate leads mastitis-related pups, resulting 100% mortality among neonates.

Language: Английский

Deep mutational scanning of H5 hemagglutinin to inform influenza virus surveillance DOI Creative Commons
Bernadeta Dadonaite, Jenny Ahn, Jordan T. Ort

et al.

PLoS Biology, Journal Year: 2024, Volume and Issue: 22(11), P. e3002916 - e3002916

Published: Nov. 12, 2024

H5 influenza is considered a potential pandemic threat. Recently, viruses belonging to clade 2.3.4.4b have caused large outbreaks in avian and multiple nonhuman mammalian species. Previous studies identified molecular phenotypes of the viral hemagglutinin (HA) protein that contribute humans, including cell entry, receptor preference, HA stability, reduced neutralization by polyclonal sera. However, prior experimental work has only measured how these are affected handful >10,000 different possible amino-acid mutations HA. Here, we use pseudovirus deep mutational scanning measure all affect each phenotype. We identify allow better bind α2-6-linked sialic acids show some already carry stabilize also sera from mice ferrets vaccinated against or infected with viruses. These antigenic maps enable rapid assessment when new strains acquired may create mismatches candidate vaccine virus, mutation present recent HAs causes change. Overall, systematic nature combined safety pseudoviruses enables comprehensive measurements phenotypic effects can inform real-time interpretation variation observed during surveillance influenza.

Language: Английский

Citations

21
Receptor Binding Specificity of a Bovine A(H5N1) Influenza Virus DOI Creative Commons
Pradeep Chopra,

Caroline Page,

Justin D. Shepard

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 31, 2024

Outbreaks in the US of highly pathogenic avian influenza virus (H5N1) dairy cows have been occurring for months creating new possibilities direct contact between and humans. Eisfeld

Language: Английский

Citations

20
A single mutation in dairy cow-associated H5N1 viruses increases receptor binding breadth DOI Creative Commons
Marina R. Good, Monica L. Fernández‐Quintero, Wei Ji

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Dec. 30, 2024

Clade 2.3.4.4b H5N1 is causing an unprecedented outbreak in dairy cows the United States. To understand if recent viruses are changing their receptor use, we screened recombinant hemagglutinin (HA) from historical and for binding to distinct glycans bearing terminal sialic acids using a glycan microarray. We find that H5 A/Texas/37/2024, isolate cow outbreak, has increased breadth core α2,3 acids, avian receptor, compared viruses. do not observe any α2,6 used by human seasonal influenza Using molecular dynamics cryo-EM structure of A/Texas/37/2024 H5, show more flexible within receptor-binding site 2022. identify single mutation outside site, T199I, responsible breadth, as it increases flexibility. Together, these data evolving which could impact host range cell types infected with H5N1.

Language: Английский

Citations

12
The impact of influenza A H5N1 virus infection in dairy cows DOI Creative Commons
F. Peña-Mosca, Elisha Frye, Matthew MacLachlan

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Abstract We investigated the impact of influenza A-H5N1 virus infection in a dairy herd. Clinical disease, which lasted for about three weeks, was recorded 20.0% (777/3,876) adult cows. Milk losses ~900 kg per cow were affected cows during 60 day-post-outbreak period. Seroprevalence 89.4% (570/637) herd, with 76.1% (485/637) seropositive animals being subclinically infected. Clinically presented an increased risk death (6 times) and premature herd removal (3.6 times), when compared to non-clinical Economic due decreased milk production, mortality early estimated at $950 clinically total cost approximately $737,500 observation Our results demonstrate long-lasting production significant financial consequences HPAI H5N1 farms.

Language: Английский

Citations

1
Receptor-binding specificity of a bovine influenza A virus DOI
Pradeep Chopra, Sean D. Ray,

Caroline Page

et al.

Nature, Journal Year: 2025, Volume and Issue: 640(8059), P. E21 - E27

Published: April 16, 2025

Language: Английский

Citations

1
ZBP1-driven cell death in severe influenza DOI
David F. Boyd, Summer Vaughn Jordan, Siddharth Balachandran

et al.

Trends in Microbiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Influenza A(H5N1) Viruses Isolated From Dairy Cattle Demonstrate High Virulence in Laboratory Models, but Retain Avian Virus-like Properties DOI Creative Commons
Richard J. Webby, Thomas Fabrizio, Ahmed Kandeil

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

Abstract In March 2024, clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) viruses were first detected in U.S. dairy cattle. Similar have since caused 66 zoonotic human infections. To assess changes to potential, we characterized isolated from cows’ milk and birds. Bovine-derived lethal mice ferrets transmitted direct but not airborne contact ferrets. All replicated bronchial epithelial cells despite preferentially binding virus-like receptors. The bovine-derived remained susceptible FDA-approved antivirals neutralized by sera vaccinated with WHO CVVs or humans 2.3.4.4c vaccine. While induce severe disease mammalian models, they retain many characteristics. Combined, conclude that the risk of contemporary affected animals is low. However, heightened vigilance remains essential promptly detect respond any changes.

Language: Английский

Citations

0
Viral Mastitis Associated with Influenza A in Dairy Cattle DOI
Patrick J. Gorden,

Drew R. Magstadt,

Amy L. Vincent Baker

et al.

Veterinary Clinics of North America Food Animal Practice, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0
Dairy cows develop protective immunity against reinfection with bovine H5N1 influenza virus DOI Creative Commons
Antonio Facciuolo, Lauren Aubrey,

Ulises Barron-Castillo

et al.

Nature Microbiology, Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

Infection of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b in dairy cows causes severe mastitis and milk production losses. Whether can develop protective immunity is unclear. Here we infected three lactating with HPAI genotype B3.13 via the hindquarters udder to mimic intra-mammary infection. Inoculated displayed clinical responses consistent affected herds United States including virus shedding almost exclusively inoculated that peaked between Days 2-4 post inoculation gradually declined by Day 21. Histologically, peak corresponded acute necrotic but not uninoculated forequarters. Two were reinfected at unaffected forequarters following resolution Secondary did result manifestations or milk. Virus-neutralizing antibodies detected 14 higher titres observed relative We also viral RNA air samples from animal rooms during routine husbandry activity. These data indicate primary infection generate against bovine cows.

Language: Английский

Citations

0
Emergence, migration and spreading of the high pathogenicity avian influenza virus H5NX of the Gs/Gd lineage into America DOI

Alejandro Aranda,

Gabriela Aguilar‐Tipacamú, Daniel R. Pérez

et al.

Journal of General Virology, Journal Year: 2025, Volume and Issue: 106(4)

Published: April 25, 2025

The high pathogenicity avian influenza virus H5N1, which first emerged in the winter of 2021, has resulted multiple outbreaks across American continent through summer 2023 and they continue based on early 2025 records, presenting significant challenges for global health food security. viruses causing belong to clade 2.3.4.4b, are descendants lineage A/Goose/Guangdong/1/1996 (Gs/Gd) genetic reassortments with several low present populations Anseriformes Charadriiformes orders. This review addresses these issues by thoroughly analysing available epidemiological databases specialized literature reviews. project explores mechanisms behind resurgence H5N1 virus. It provides a comprehensive overview origin, timeline factors contributing its prevalence among wild bird continent.

Language: Английский

Citations

0