Replication Kinetics, Pathogenicity and Virus-induced Cellular Responses of Cattle-origin Influenza A(H5N1) isolates from Texas, United States DOI Creative Commons
Elsayed M. Abdelwhab, Ramya S. Barre, Anna Allué‐Guardia

et al.

Emerging Microbes & Infections, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 27, 2024

The host range of HPAIV H5N1 was recently expanded to include ruminants, particularly dairy cattle in the United States (US). Shortly after, human infection reported a worker Texas following exposure infected cattle. Herein, we rescued cattle-origin influenza A/bovine/Texas/24-029328-02/2024(H5N1, rHPbTX) and A/Texas/37/2024(H5N1, rHPhTX) viruses, identified human, respectively, their low pathogenic forms, rLPbTX rLPhTX, with monobasic HA cleavage sites. Intriguingly, rHPhTX replicated more efficiently than rHPbTX mammalian avian cells. Still, variations PA NA proteins didn't affect antiviral susceptibility inhibitors. Unlike rLPbTX, both rLPhTX exhibited higher pathogenicity efficient replication C57BL/6J mice. lungs rHPhTX-infected mice produced inflammatory cytokines/chemokines rHPbTX-infected Our results highlight potential risk virus adaptation and/or during current multistate/multispecies outbreak US.

Language: Английский

Highly Pathogenic Avian Influenza A (H5N1) clade 2.3.4.4b Virus detected in dairy cattle DOI Creative Commons
Xiao Hu, Anugrah Saxena,

Drew R. Magstadt

et al.

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

Published: April 16, 2024

Abstract The global emergence of highly pathogenic avian influenza (HPAI) A (H5N1) clade 2.3.4.4b viruses poses a significant public health threat. Until March 2024, no outbreaks this virus had occurred in domestic cattle. We genetically characterize HPAI from dairy cattle showing an abrupt drop milk production. They share nearly identical genome sequences, forming new genotype B3.13 within the clade. underwent two reassortment events since 2023 and exhibit critical mutations HA, M1, NS genes but lack PB2 PB1 genes, which enhance virulence or adaptation to mammals. E627K mutation human case underscores potential for rapid evolution post-infection, highlighting need continued surveillance monitor threats.

Language: Английский

Citations

30

Genomic characterization of highly pathogenic avian influenza A H5N1 virus newly emerged in dairy cattle DOI Creative Commons
Xiao Hu, Anugrah Saxena,

Drew R. Magstadt

et al.

Emerging Microbes & Infections, Journal Year: 2024, Volume and Issue: 13(1)

Published: July 15, 2024

In March 2024, the emergence of highly pathogenic avian influenza (HPAI) A (H5N1) infections in dairy cattle was detected United Sates for first time. We genetically characterize HPAI viruses from showing an abrupt drop milk production, as well two cats, six wild birds, and one skunk. They share nearly identical genome sequences, forming a new genotype B3.13 within 2.3.4.4b clade. underwent reassortment events since 2023 exhibit critical mutations HA, M1, NS genes but lack PB2 PB1 genes, which enhance virulence or adaptation to mammals. The E627 K mutation human case associated with underscores potential rapid evolution post infection, highlighting need continued surveillance monitor public health threats.

Language: Английский

Citations

20

The avian and human influenza A virus receptors sialic acid (SA)-α2,3 and SA-α2,6 are widely expressed in the bovine mammary gland DOI Creative Commons
Charlotte Kristensen, Henrik Elvang Jensen, Ramona Trebbien

et al.

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

Published: May 3, 2024

Abstract An outbreak of H5N1 highly pathogenic influenza A virus (HPIAV) has been detected in dairy cows the United States. Influenza (IAV) is a negative-sense, single-stranded, RNA that not previously associated with widespread infection cattle. As such, cattle are an extremely under-studied domestic IAV host species. receptors on cells sialic acids (SAs) bound to galactose either α2,3 or α2,6 linkage. Human IAVs preferentially bind SA-α2,6 (human receptor), whereas avian have preference for (avian receptor). The receptor can further be divided into two receptors: isolated from chickens generally more tightly SA-α2,3-Gal-β1,4 (chicken duck SA-α2,3-Gal-β1,3 (duck We found all were expressed, different degree, mammary gland, respiratory tract, and cerebrum beef and/or human widely expressed bovine chicken dominated tract. In general, only low expression was observed neurons cerebrum. These results provide mechanistic rationale high levels reported infected milk show potential act as mixing vessel novel generation. Graphical abstract Created Biorender.com

Language: Английский

Citations

18

Preparedness, prevention and control related to zoonotic avian influenza DOI Creative Commons
Julio Álvarez, Anette Boklund, Sabine Dippel

et al.

EFSA Journal, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 1, 2025

A risk assessment framework was developed to evaluate the zoonotic potential of avian influenza (AI), focusing on virus mutations linked phenotypic traits related mammalian adaptation identified in literature. Virus sequences were screened for presence these and their geographical, temporal subtype-specific trends. Spillover events mammals (including humans) human seroprevalence studies also reviewed. Thirty-four associated with five (increased receptor specificity, haemagglutinin stability, neuraminidase enhanced polymerase activity evasion innate immunity) shortlisted. AI viruses (AIVs) carrying multiple adaptive belonged both low highly pathogenic subtypes, mainly A(H9N2), A(H7N9), A(H5N6) A(H3N8), sporadic primarily detected Asia. In EU/EEA, H5Nx clade 2.3.4.4b, which have increased opportunities evolution due widespread circulation birds occasional cases/outbreaks mammals, acquired highest number traits. Adaptive traits, such as immune evasion, frequently acquired, while receptor-specific remained rare. Globally, cases remain rare, majority overall A(H5N1), A(H5N6), A(H7N9) A(H9N2) that are among subtypes tend a higher The main drivers include host characteristics, external factors increasing AIV exposure humans wild domestic (e.g. activities ecological factors). Comprehensive surveillance AIVs targeting whole genome sequencing animals is essential early detection efficient implementation control measures. All preparedness, preventive measures must be implemented under One Health tailored setting epidemiological situation; particular, monitoring, biosecurity, genomic global collaboration critical mitigating risks AIV.

Language: Английский

Citations

2

Highly Pathogenic Avian Influenza Virus A(H5N1) Clade 2.3.4.4b Infection in Free-Ranging Polar Bear, Alaska, USA DOI Creative Commons
Raphaela Stimmelmayr, David S. Rotstein, Mia Kim Torchetti

et al.

Emerging infectious diseases, Journal Year: 2024, Volume and Issue: 30(8)

Published: July 1, 2024

We report a natural infection with Eurasian highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus in free-ranging juvenile polar bear (Ursus maritimus) found dead North Slope Borough, Alaska, USA. Continued community and hunter-based participation wildlife health surveillance is key to detecting emerging pathogens the Arctic.

Language: Английский

Citations

9

Baloxavir improves disease outcomes in mice after intranasal or ocular infection with Influenza A virus H5N1-contaminated cow’s milk DOI
Jeremy C. Jones, Konstantin Andreev, Thomas Fabrizio

et al.

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

Published: March 17, 2025

Language: Английский

Citations

1

Olfactory immune response to SARS-CoV-2 DOI Creative Commons
Sebastian A. Wellford, E. Ashley Moseman

Cellular and Molecular Immunology, Journal Year: 2023, Volume and Issue: 21(2), P. 134 - 143

Published: Dec. 25, 2023

Abstract Numerous pathogens can infect the olfactory tract, yet pandemic caused by SARS-CoV-2 has strongly emphasized importance of mucosa as an immune barrier. Situated in nasal passages, is directly exposed to environment sense airborne odorants; however, this also means it serve a direct route entry from outside world into brain. As result, olfactotropic infections have serious consequences, including dysfunction system, CNS invasion, dissemination lower respiratory and transmission between individuals. Recent research shown that distinctive response needed protect neuronal mucosal tissue. A better understanding innate, adaptive, structural barriers develop effective therapeutics vaccines against microbes such SARS-CoV-2. Here, we summarize ramifications infection mucosa, review subsequent response, discuss important areas future for immunity infectious disease.

Language: Английский

Citations

16

Recent Bovine HPAI H5N1 Isolate Is Highly Virulent For Mice, Rapidly Causing Acute Pulmonary And Neurologic Disease DOI Creative Commons
Thomas Tipih, Vignesh Mariappan, Claude Kwe Yinda

et al.

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

Published: Aug. 19, 2024

Abstract The highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b viruses, responsible for the current outbreak in dairy cows United States, pose a significant animal and public health threat. In this study, we compared disease progression pathology of three recent isolates derived from cow, mountain lion, mink to human HPAI isolate Vietnam mice. Inoculation C57BL/6J BALB/c mice with all four resulted comparable levels virus replication lung inducing severe respiratory disease. infected bovine also developed high titers brain, resulting pro-inflammatory cytokine response neurologic Our findings suggest possesses enhanced neuroinvasive/neurovirulent properties causing fatal

Language: Английский

Citations

4

Reverse genetics-derived cattle H5N1 virus from Clade 2.3.4.4b shows enhanced systemic infectivity and pathogenicity than an older Clade 1 H5N1 virus in BALB/c mice DOI Creative Commons
Na Xiao, Xiang Yong Oong, Yanxia Chen

et al.

Emerging Microbes & Infections, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

The newly emerged avian influenza A H5N1 Clade 2.3.4.4b can infect dairy cows and shed live virus in their milk. Sporadic cattle-to-human infections have been reported, highlighting the urgent need to understand its pathogenesis mammals. Using both non-lactating lactating BALB/c mice, we examined viral tissue tropism, histopathological damages, host immune responses upon intranasal inoculation with a reverse-genetic constructed based on A/dairy cattle/Texas/24-008749-003/2024 (Cattle-H5N1) comparing an older reference 1 virus, A/Vietnam/1194/2004 (VNM1194-H5N1). Cattle-H5N1 was highly lethal mice (mLD50 =1.48PFU) broad tropism produced higher titer respiratory multiple extrapulmonary organs than VNM1194-H5N1. In lungs, infection of airway epithelium, type II pneumocytes CD45+ cells were at frequency those VNM1194-H5N1-infected resulting severe epithelial destruction diffuse alveolar damage accompanied by elevated lung serum pro-inflammatory cytokine/chemokines. Although viruses showed mammary gland more severely damaged after abundant antigens expression glandular cells, associated fat lymphoid tissues. Furthermore, suckling co-housed infected virus-positive (7/30 pups) Brains heavily Cattle-H5N1, neurological signs such as body-rolling/spinning, trembling and/or limb paralysis seen only mice. spleen infection, which massive antigen apoptosis splenic atrophy, concluding that is virulent

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