Rapid #Expansion of Highly Pathogenic Avian #Influenza #H5N1 Clade 2.3.4.4b Genotype #D1.1 Virus across #Flyway Regions, North #America, Fall 2024

 

Abstract

Highly pathogenic avian influenza clade 2.3.4.4b virus continues to circulate in North America and has caused severe human disease. That clade includes genotype D1.1, which became dominant in birds in late 2024. Recent phylodynamic reconstructions place D1.1 emergence in mid-2024 but differ on its inferred origin and early dissemination pathways. We combined targeted surveillance of wild birds in Arizona with publicly available US clade 2.3.4.4b hemagglutinin sequences to estimate when D1.1 genotype emerged and to infer its diffusion among the 4 major US flyways. Phylodynamic analyses showed transitions concentrated among adjacent flyways regions, consistent with stepwise dissemination during fall 2024 and limited support for long-distance Pacific–Atlantic exchange. The Pacific Flyway showed patterns consistent with an early source and the Central Flyway with a secondary hub linked to onward spread. Our findings support coordinated genomic surveillance across adjacent flyways to reduce detection delays and improve situational awareness during rapid viral expansion.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/8/26-0205_article

____

Highly Pathogenic Avian #Influenza #H5N1 in South #America, 2022–2025: Spread, Affected Species, and Southward Expansion into the #Antarctic Region

 

Abstract

The H5N1 highly pathogenic avian influenza (HPAI) virus has caused severe global losses, reaching South America in 2022 and Antarctica in 2024. Here, we synthesize outbreak reports submitted to the World Organization for Animal Health by South American countries and overseas territories in this continent, and document the virus’s unprecedented expansion into Antarctica, affecting wild birds, wild mammals, and domestic poultry. Phylogenetic and time-calibrated Bayesian analyses were performed on available genomic sequences. Over 6 million domestic birds were lost, mostly from commercial operations. Of the 11 South American countries and overseas territories that reported H5N1 to WOAH, 10 reported infections in wild birds, spanning 104 species, 59.62% of which are migratory and predominantly non-trans-equatorial. Marine mammal outbreaks followed wild bird detections, with the South American sea lion (Otaria flavescens) being the most reported species. Several Antarctic bird species with migratory behavior were also reported in South America. Genomic analyses revealed multiple introduction events, regional viral diversification, and patterns consistent with repeated cross-species spillover events. These findings highlight H5N1’s extensive ecological reach in the Southern Hemisphere and underscore the urgent need for a One Health approach that strengthens wildlife and backyard-poultry surveillance, alongside coordinated regional action to control and prevent further HPAI spread.

Source: 

Link: https://www.mdpi.com/1999-4915/18/7/764

____

#MHC-II acts as a #fusion-triggering #receptor for #bat #influenza virus

 

Abstract

Influenza A virus hemagglutinin is a prototypical class I viral fusion protein that binds sialylated glycans and is activated by low pH in endosomes. In contrast, bat-derived IAV subtypes H17N10 and H18N11 use major histocompatibility complex class II (MHC-II) as an entry receptor, but how this receptor contributes to membrane fusion remains unknown. We find that MHC-II-dependent hemagglutinin subtypes H17, H18, and H19 possess an increased negative net charge relative to canonical HAs. Using cryo-electron tomography, we demonstrate that H18N11 morphology remains stable and H18 is in prefusion conformation at strongly acidic pH. Remarkably, H18 undergoes fusion-relevant conformational changes only when both MHC-II binding and low pH are present. By reconstitution of H18N11 fusion with liposomes and purified MHC-II, we show that receptor engagement is required to trigger the fusion activity of H18. These findings identify MHC-II as a receptor that directly triggers membrane fusion and reveal a previously unrecognized receptor-dependent mechanism of influenza virus entry.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Deutsche Forschungsgemeinschaft, https://ror.org/018mejw64, 240245660 – P19, 537227910

European Research Council, 882631—Bat Flu

Excellence Initiative of the German Research Foundation, GSC-4, Spemann Graduate School

Hans A. Krebs Medical Scientist Programme

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.07.08.737388v1

____

Lactylation of #Influenza Virus #Polymerase Acidic Protein Promotes Viral #Replication and #Pathogenicity

 

Abstract

Influenza virus poses a potential risk of triggering the next global pandemic. In-depth investigation into the mechanisms underlying influenza virus replication and pathogenicity will provide robust support for controlling influenza virus infection. Although post-translational modifications are known to regulate viral infection, the role of lactylation in influenza virus replication remains elusive. In this study, influenza virus ribonucleoprotein complex subunits are found to be lactylated. Specifically, ATAT1 promotes viral polymerase acidic protein (PA) lactylation and enhances viral replication. In contrast, SIRT1 mediates de-lactylation of PA and exerts an inhibitory effect on viral replication. Further investigations reveal lactylation of PA at residues K605 and K609 is essential for viral replication and pathogenicity. Mechanistically, PA K605/609 residues are localized at the interaction interface of the ANP32-mediated polymerase asymmetric dimer; mutation at these residues inhibits polymerase asymmetric dimerization, thereby impairing RNA production during viral genome replication. Collectively, this study uncovers a novel mechanism by which influenza virus hijacks host enzymes to mediate PA lactylation, and expands the molecular regulatory network of influenza virus infection.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.07.10.737663v1

____

Long-Term #Monitoring of #Influenza A Viruses in Wild #Waterfowl: Evidence from the Lake #Baikal Basin (2018–2024)

 

Abstract

Wild waterfowl constitute the primary natural reservoir of influenza A viruses, and wetlands at the convergence of major migratory flyways serve as critical hubs for viral genetic exchange. Baikal Siberia, situated at the intersection of the East African–West Asian, Central Asian, and East Asian–Australasian flyways, represents a unique yet understudied region in this context. Here we report the results of long-term virological surveillance of wild birds in the Lake Baikal basin conducted between 2018 and 2024. A total of 1036 cloacal swab samples from 28 bird species were screened, yielding 42 influenza A virus isolates belonging to 12 HA/NA subtype combinations: H1N1, H3N1, H3N2, H3N5, H3N6, H3N8, H4N6, H6N1, H6N2, H6N3, H6N8, and H12N5. Among the detected subtypes, H6 viruses—identified with four distinct neuraminidase combinations (N1, N2, N3, N8)—are of particular public health relevance owing to their documented capacity for dual-receptor binding and potential for zoonotic transmission to mammals, including humans. Full-genome sequencing followed by cluster analysis of internal gene segments identified 16 distinct segment constellations, indicating extensive reassortment. BLAST searches against the GISAID database revealed closest genetic relatives in Mongolia, South Korea, Japan, China, and Western Siberia, with more distant links to Bangladesh, Europe, and a possible intercontinental connection via the Pacific flyway. Maximum-likelihood phylogenetic analysis of the HA and NA segments confirmed that all isolates belong to the Eurasian genetic lineage, yet they are distributed across multiple clades rather than forming a single monophyletic group, reflecting the role of Buryatia as a mixing zone for genetically diverse viral populations. These findings substantially expand the understanding of influenza A virus ecology in the Lake Baikal basin and underscore the importance of continued surveillance at this key migratory crossroads in Northern Asia.

Source: 

Link: https://www.mdpi.com/1999-4915/18/7/761

____

Preparing for the Next #Pandemic: Learning From #COVID19 to Build What Comes Next

 

Abstract

WHO's efforts to strengthen pandemic preparedness—grounded in what the world learned during COVID-19 and what today's outbreaks of avian influenza, Hantavirus and Ebola are teaching us.

Source: 

Link: https://academic.oup.com/ofid/article/13/7/ofag348/8728458

____

#Coronavirus Disease Research #References (AMEDEO, July 11 '26)

 

Am J Respir Crit Care Med

1. JERRETT M, Nau CL, Young DR, Butler RK, et al
   Association Between Air Pollution and Post Acute Sequelae of SARS-CoV-2 (PASC).
   Am J Respir Crit Care Med. 2026 Jul 3:aamag341. doi: 10.1093.
   PubMed        
   
   

   
   Ann Intern Med

2. DARNALL BD, Perez L, Kao MC, Lorig K, et al
   Patient-Centered Prescription Opioid Tapering Methods : A Randomized Clinical Trial.
   Ann Intern Med. 2026 Jul 7. doi: 10.7326/ANNALS-25-04784.
   PubMed         Abstract available
   
   

   
   BMJ

3. HAQ ZU
   Ebola control is weakened by mistrust and cultural insensitivity.
   BMJ. 2026;394:e100190.
   PubMed        
   
   

   
   Clin Infect Dis

4. ROSTER KIO, White PJ, Grad YH
   Why Are Gonorrhea Case Rates Declining in the United States? A Research Agenda.
   Clin Infect Dis. 2026;82:1082-1090.
   PubMed         Abstract available
   
   

   
   Int J Infect Dis

5. MIYAKAWA K, Sano K, Seki Y, Sato R, et al
   Cross-neutralization of SARS-CoV-2 BA.3.2.2 lineage by JN.1 mRNA vaccine-induced immunity.
   Int J Infect Dis. 2026 Jul 4:108954. doi: 10.1016/j.ijid.2026.108954.
   PubMed         Abstract available
   
   
6. JO Y, Hu Z, Joo H, Jung J, et al
   Time to Recovery from Long COVID: A Longitudinal Analysis of Symptom Duration and Risk Factors Using Accelerated Failure Time Models.
   Int J Infect Dis. 2026 Jul 5:108963. doi: 10.1016/j.ijid.2026.108963.
   PubMed         Abstract available
   
   
7. CHUI CSL, Lau JC, Fan M, Chan BP, et al
   Concurrent comparison of severity of influenza and COVID-19 among hospitalized patients in Hong Kong: a target trial emulation on observational healthcare data.
   Int J Infect Dis. 2026 Jul 7:108958. doi: 10.1016/j.ijid.2026.108958.
   PubMed         Abstract available
   
   
8. JABER F, Rawas SE, Faraj S, Zoghby LA, et al
   Value of the Pitt bacteremia score in predicting the outcome of non-bacteremic patients with infections caused by multidrug-resistant organisms.
   Int J Infect Dis. 2026 Jul 7:108960. doi: 10.1016/j.ijid.2026.108960.
   PubMed         Abstract available
   
   
9. ACANFORA D, Nolano M, Acanfora C, Colella C, et al
   Vagal cholinergic denervation of the gastric mucosa in Long-COVID-19: in vivo evidence of structural autonomic dysfunction.
   Int J Infect Dis. 2026 Jul 9:108973. doi: 10.1016/j.ijid.2026.108973.
   PubMed         Abstract available
   
   

   
   J Infect

10. VINK E, Murphy ME, Gunson R, MacConnachie A, et al
    Respiratory viral detection in adult severe acute respiratory infection post-COVID-19 pandemic: implications for antimicrobial stewardship.
    J Infect. 2026;93:106805.
    PubMed         Abstract available
    
    

    
    J Med Virol

11. BUMBERGER AM, Kastner MT, Gawish R, Rusing L, et al
    Torque Teno Virus Dynamics in Plasma and BAL of COVID-19 ARDS Patients With and Without ECMO.
    J Med Virol. 2026;98:e71047.
    PubMed         Abstract available
    
    
12. WENINGER J, Zedginidze A, Katsounas A, Pohl M, et al
    Assessment of Residual-Serum SARS-CoV-2-N-Antigen Testing for Hospital Surveillance in Germany.
    J Med Virol. 2026;98:e71055.
    PubMed         Abstract available
    
    
13. GORIS M, Valdez M, Lamont L, Yang W, et al
    Tracking COVID-19 Severity and Progression Through Amines and Lipid Mediators.
    J Med Virol. 2026;98:e71030.
    PubMed         Abstract available
    
    
14. TUNER B, Agca H
    Molecular Types of Rhinovirus Among Cases of Acute Respiratory Infections in a University Hospital.
    J Med Virol. 2026;98:e71058.
    PubMed         Abstract available
    
    

    
    J Virol

15. LIANG Y-F, Li X, Zhu G-x, Song Y, et al
    Magnolol inhibits porcine epidemic diarrhea virus infection by suppressing cathepsin L expression in vitro and in vivo.
    J Virol. 2026 Jun 25:e0013726. doi: 10.1128/jvi.00137.
    PubMed         Abstract available
    
    
16. ZHAO Y, Zhao J, Li Y, Duan L, et al
    Disruption of the S1/S2 multibasic cleavage site attenuates infectious bronchitis virus, while S2' partially restores viral virulence and expands tissue tropism.
    J Virol. 2026 Jul 6:e0061426. doi: 10.1128/jvi.00614.
    PubMed         Abstract available
    
    
17. STEFANOS B, Green NRB, Nadig I, Lapierre LA, et al
    Coronavirus membrane protein with a fluorescent protein tag enables particle tracking for the study of virus assembly and egress in live cells.
    J Virol. 2026 Jul 6:e0222825. doi: 10.1128/jvi.02228.
    PubMed         Abstract available
    
    
18. ZHOU R, Yue M, Shen Q, Liu N, et al
    Glucagon-like peptide-1 receptor agonist prevents pulmonary fibrosis following acute COVID-19 infection associated with type 2 diabetes.
    J Virol. 2026 Jul 9:e0040126. doi: 10.1128/jvi.00401.
    PubMed         Abstract available
    
    

    
    Lancet

19. DEZZA FC, Pulido LB, Borreguero IB, Perez FD, et al
    Temocillin versus carbapenems for bacteraemia due to third-generation cephalosporin-resistant Enterobacterales in Spain (ASTARTE): a multicentre, phase 3, open-label, non-inferiority, randomised clinical trial.
    Lancet. 2026 Jul 9:S0140-6736(26)00760-9. doi: 10.1016/S0140-6736(26)00760.
    PubMed         Abstract available
    
    

    
    Lancet Infect Dis

20. 
    Efficacy and safety of rivaroxaban, colchicine, and famotidine-loratadine with specialist supportive clinical care for fatigue in patients with post-COVID-19 condition in the UK: a multisite, open-label, randomised controlled trial.
    Lancet Infect Dis. 2026 Jul 8:S1473-3099(26)00242.
    PubMed         Abstract available
    
    

    
    MMWR Morb Mortal Wkly Rep

21. PATRICK R, Lee K, Kuan M, Chan M, et al
    Norovirus, COVID-19, and Influenza Outbreaks Among Residents and Staff Members at the Eaton Wildfire Evacuation Shelter - Pasadena, California, January-February 2025.
    MMWR Morb Mortal Wkly Rep. 2026;75:337-342.
    PubMed         Abstract available

#Influenza and Other Respiratory Viruses Research #References (AMEDEO, July 11 '26)

 

BMC Pediatr

1. HEIBA D, Salem N, Antonios M, Shoman W, et al
   Comparative study of post- COVID-19 Kawasaki disease and multisystem inflammatory syndrome cases at Alexandria University Children's Hospital.
   BMC Pediatr. 2026;26:644.
   PubMed         Abstract available
   
   
2. LIN C, Zhu Z, Li Y, Wei J, et al
   Diagnostic value of cytokine detection in children with Mycoplasma pneumoniae pneumonia complicated by bacterial or viral co-infections.
   BMC Pediatr. 2026;26:629.
   PubMed         Abstract available
   
   

   
   Epidemiol Infect

3. DAVOODI Z, Laurie C, Tingley K, Skidmore B, et al
   Risk-of-bias assessment of vaccine effectiveness studies: a scoping review of systematic reviews.
   Epidemiol Infect. 2026;154:e95.
   PubMed         Abstract available
   
   
4. ROSCA EC, Oke J, Jefferson T, Brassey J, et al
   Serial cycle threshold to assess the infectious potential of SARS-CoV-2: A systematic review.
   Epidemiol Infect. 2026;154:e89.
   PubMed         Abstract available
   
   

   
   J Clin Microbiol

5. MCTAGGART LR, Eshaghi A, Cronin K, Patel SN, et al
   Post-pandemic surge of Mycoplasma pneumoniae in Ontario, 2024: molecular surveillance and resistance trends relative to 2018-2023.
   J Clin Microbiol. 2026;64:e0018826.
   PubMed         Abstract available
   
   

   
   J Infect

6. LI Y, Zhang T, Gao J
   Home-Based Rapid Testing and Early Antiviral Treatment as a Potential Strategy to Blunt Pediatric Influenza Peak.
   J Infect. 2026 Jul 7:106807. doi: 10.1016/j.jinf.2026.106807.
   PubMed        
   
   

   
   J Infect Dis

7. SKELLINGTON CN, Schmidt K, Schofield C, Ganesan A, et al
   The Effect of Prevaccination Analgesics on Influenza Vaccine Immunogenicity and Effectiveness.
   J Infect Dis. 2026 Jul 10:jiag334. doi: 10.1093.
   PubMed         Abstract available
   
   

   
   J Virol

8. JIA H, Lin C, Guo Y, Cai W, et al
   A neuraminidase-targeted nanobody confers broad protection against influenza B virus.
   J Virol. 2026 Jul 10:e0076226. doi: 10.1128/jvi.00762.
   PubMed         Abstract available
   
   
9. BARRON-CASTILLO U, Berube N, Swan CL, Javed MA, et al
   Receptor profiling and growth assessment of influenza A virus in porcine mammary and non-mammary tissues and derived cells.
   J Virol. 2026 Jul 6:e0061526. doi: 10.1128/jvi.00615.
   PubMed         Abstract available
   
   

   
   MMWR Morb Mortal Wkly Rep

10. PATRICK R, Lee K, Kuan M, Chan M, et al
    Norovirus, COVID-19, and Influenza Outbreaks Among Residents and Staff Members at the Eaton Wildfire Evacuation Shelter - Pasadena, California, January-February 2025.
    MMWR Morb Mortal Wkly Rep. 2026;75:337-342.
    PubMed         Abstract available
    
    

    
    Pediatrics

11. LEONARD JS, Reinhart K, Lu PJ, Santibanez TA, et al
    Influenza Vaccine Effectiveness Against Pediatric Death in the United States: 2016-2025.
    Pediatrics. 2026 Jul 6:e2026076453. doi: 10.1542/peds.2026-076453.
    PubMed         Abstract available
    
    
12. HAHN C, Sardi A, Ratner AJ
    Averting the Unthinkable: Immunization to Prevent Childhood Deaths From Influenza.
    Pediatrics. 2026 Jul 6:e2026076867. doi: 10.1542/peds.2026-076867.
    PubMed        
    
    

    
    PLoS Comput Biol

13. WANG B, Valdano E
    Redefining and estimating the early-phase reproduction ratio for epidemic outbreaks in spatially structured populations.
    PLoS Comput Biol. 2026;22:e1014425.
    PubMed         Abstract available
    
    

    
    PLoS One

14. LI W, Tan HL, Zhuang CY, Li JY, et al
    Parental knowledge, vaccine hesitancy, and practices regarding seasonal influenza vaccination for preschool-aged children in Shenzhen, China: Insights from a cross-sectional survey.
    PLoS One. 2026;21:e0353478.
    PubMed         Abstract available
    
    
15. SANOGO IN, Puryear WB, Simulynas AF, DiGiovanni R, et al
    Serological evidence of SARS-CoV-2 exposure in marine mammals in the United States between 2020 and 2025.
    PLoS One. 2026;21:e0351734.
    PubMed         Abstract available
    
    
16. HIRATA K, Chiba T, Takaku R, Meilai C, et al
    Beyond the freedom to refuse patient: A retrospective comparative study of emergency transportation during the COVID-19 pandemic in Japan.
    PLoS One. 2026;21:e0331535.
    PubMed         Abstract available
    
    
17. HAKKI S, Nevin S, Conibear E, Madon KJ, et al
    Full blood count dynamics in immunologically naive individuals with mild COVID-19: A prospective community cohort study.
    PLoS One. 2026;21:e0353142.
    PubMed         Abstract available
    
    
18. BURCHARDI JM, Brunger M, Freitag H, Brock A, et al
    Improving the care of people affected by post-COVID syndrome (LCovB):study protocol of a mixed-methods study.
    PLoS One. 2026;21:e0353270.
    PubMed         Abstract available
    
    
19. AL-AGHBARI N
    Serum albumin and blood urea as independent predictors of in-hospital mortality in hospitalized COVID-19 patients: A retrospective cohort study.
    PLoS One. 2026;21:e0353456.
    PubMed         Abstract available
    
    
20. JEWELL M, Marye A, Barbeau B, Oakeson K, et al
    Beyond traditional outbreak investigation: Using genomic data for enhanced detection of COVID-19 disease clusters in Utah.
    PLoS One. 2026;21:e0342637.
    PubMed         Abstract available
    
    
21. IIDA K, Mori H, Remez D, Krokva D, et al
    Epidemiological characteristics of amebiasis in Japan from 2001 to 2022.
    PLoS One. 2026;21:e0318901.
    PubMed         Abstract available
    
    
22. FREDERIKSEN L, Subedi S, Choong K, Anderson J, et al
    Respiratory and bloodstream coinfections and antimicrobial use in hospitalised patients with moderate to severe COVID-19: An Australian retrospective cohort study.
    PLoS One. 2026;21:e0352344.
    PubMed         Abstract available
    
    
23. FUKUDA T, Haruyama R, Tanaka Y, Natori S, et al
    Development of a COVID-19 Vaccination Anxiety Scale to measure COVID-19 vaccine anxiety in Japanese adults.
    PLoS One. 2026;21:e0330146.
    PubMed         Abstract available
    
    
24. MICHALAKI E, Van Zanten A, Najjar J, Byagathvalli G, et al
    A piezoelectric electroporator (Piezopen) for enhanced "naked" RNA vaccine delivery.
    PLoS One. 2026;21:e0353214.
    PubMed         Abstract available
    
    
25. GACH D, van Osch FHM, van den Bergh JP, Posthuma R, et al
    Long-term multidimensional health status of individuals with and without post COVID-19 condition: A cross-sectional study.
    PLoS One. 2026;21:e0352332.
    PubMed         Abstract available
    
    
26. CONGDON C, Malik F, Jina R, Kumar D, et al
    A multi-country qualitative evaluation of rapid mortality surveillance during the COVID-19 pandemic.
    PLoS One. 2026;21:e0333157.
    PubMed         Abstract available
    
    

    
    Vaccine

27. ZHANG L, Lin T, Wang M, Ma X, et al
    Retraction notice to "Effectiveness of prescription-based influenza vaccination services among older adults in Binzhou, China: A cluster-randomized controlled trial" [Vaccine 82 (2026) 128588].
    Vaccine. 2026 Jul 6:128885. doi: 10.1016/j.vaccine.2026.128885.
    PubMed        

Isolation and characterization of a clade 2.3.4.4b genotype #D1.1 #H5N1 virus from dairy #cattle in #Wisconsin

 

ABSTRACT

Highly pathogenic avian influenza A(H5N1) (HPAI H5N1) viruses of clade 2.3.4.4b have recently been detected in U.S. dairy cattle following multiple spillover events from avian reservoirs. In December 2025, HPAI H5N1 virus was identified in a dairy herd in Wisconsin through the National Milk Testing Strategy. Here, we report the isolation of a clade 2.3.4.4b, genotype D1.1 H5N1 virus, A/dairy cow/Wisconsin/25G05743-001/2025 (WI5743-H5N1), from bulk milk associated with the affected herd, describe its phylogenetic relationships, and assess its pathogenicity in mice. Infectious virus was recovered following blind passage in embryonated chicken eggs. Phylogenetic analysis demonstrated that WI5743-H5N1 is distinct from previously reported D1.1 viruses detected in dairy cattle in Nevada and Arizona, supporting an independent introduction into cattle, and indicating a likely local avian source. Compared with closely related avian viruses, WI5743-H5N1 encoded the mammalian-adapting substitution PB2-E627K and additional amino acid differences in HA, PB1-F2, and NS1. In mice, WI5743-H5N1 replicated efficiently in respiratory tissues and was detectable in the brain but exhibited lower lethality relative to other recent clade 2.3.4.4b, genotype B3.13 viruses. Together, these findings highlight the genetic and phenotypic diversity of HPAI H5N1 viruses infecting dairy cattle and underscore the importance of continued surveillance and functional characterization of emerging strains.

IMPORTANCE

Highly pathogenic avian influenza A(H5N1) viruses have recently entered U.S. dairy cattle through multiple spillover events from avian reservoirs, creating new opportunities for viral adaptation in mammals. Here, we describe the isolation and characterization of a clade 2.3.4.4b, genotype D1.1 H5N1 virus from bulk milk collected during a spillover event in Wisconsin in December 2025. Phylogenetic analyses demonstrated that this virus represents an independent introduction into dairy cattle distinct from previously reported D1.1 viruses identified in Nevada and Arizona. Although the virus encoded the mammalian-adapting PB2-E627K substitution, it exhibited comparatively low lethality in mice, highlighting the complexity of mammalian adaptation and pathogenicity in H5N1 viruses. These findings expand current understanding of the genetic and phenotypic diversity of H5N1 viruses infecting dairy cattle and emphasize the importance of continued surveillance and functional characterization of emerging strains.

Source: 

Link: https://journals.asm.org/doi/10.1128/jvi.00761-26

____

Navigating the #Panzootic Era of HPAI #H5N1: Bridging #Surveillance and #Countermeasure Deficits

 

{Excerpt}

The evolutionary trajectory of highly pathogenic avian influenza (HPAI) H5N1 has fundamentally shifted from a sporadic agricultural pathogen to an enduring global panzootic. Since the emergence of the 2.3.4.4b clade in late 2020, the virus has transcended its traditional localized agricultural disruptions to establish endemic circulation within wild bird reservoirs across all inhabited continents, including recent, unprecedented incursions into the sub-Antarctic and Antarctic regions as well as Oceania. This dramatic expansion in host plasticity has enabled the virus to infect over seventy distinct mammalian species, triggering catastrophic mortality events in marine mammals across South America and widespread, unprecedented outbreaks within commercial dairy cattle herds in the United States. 

(...)

Source: 

Link: https://www.mdpi.com/1999-4915/18/7/757

____

Isolation of Infectious Highly Pathogenic Avian #Influenza #H5N1 Virus from #Fetal #Bovine Serum, #USA, 2025

 

Abstract

In February 2025, we detected highly pathogenic avian influenza virus A(H5N1) clade 2.3.4.4b virus in a fetal bovine serum lot during routine adventitious agent testing. Sequencing confirmed H5N1 genotype B3.13 virus. We found low viral loads in additional samples from the same lot. Heating at 56°C for 30 minutes completely inactivated the virus.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/8/26-0077_article

____

#Cattle and #human #organoids reveal 2.3.4.4b #H5N1 cross-species #transmission potential and #neuraminidase-specific neutralizing #antibodies in humans

 

Abstract

The unexpected circulation of clade 2.3.4.4b H5N1 influenza viruses in dairy cattle and the transmission to diverse mammalian species poses a pandemic risk. We sought to explore cattle and human respiratory susceptibility to the 2.3.4.4b H5N1 virus. We establish long-term expandable cattle airway and mammary organoids. The 2.3.4.4b H5N1 virus exhibits high replicative fitness in cattle mammary organoids, recapitulating its remarkable mammary tropism. The virus also replicates robustly in cattle airway organoids, suggesting an underrecognized respiratory component in ongoing outbreaks. Interestingly, human airway and nasal organoids are highly susceptible to the 2.3.4.4b H5N1 virus. Yet, a novel organoid-based neutralization assay reveals that N1 antibodies in human sera had cross-neutralizing activity against the 2.3.4.4b H5N1 and ancestral H5N1-VN1194 viruses. The cross-neutralization, exclusively manifested in the organoid-based assay, is enhanced after seasonal influenza vaccination and diminished after depleting N1-specific antibodies. Therefore, cross-neutralizing N1 antibodies are likely limiting zoonotic infection by H5N1 viruses in humans.

Source: 

Link: https://www.nature.com/articles/s41467-026-74345-w

____

Characterization of #oseltamivir-resistant #H5N1 clade 2.3.4.4b, genotype #D1.1 #variants identified in #poultry farms of British Columbia, #Canada

 

ABSTRACT

Highly pathogenic avian influenza A(H5N1) viruses of clade 2.3.4.4b, genotype D1.1, are responsible for widespread outbreaks in poultry and continue to cause sporadic, sometimes severe, human infections. Herein, we characterized a wild-type (WT) influenza A(H5N1) D1.1 isolate (BC-H5N1-WT) and its H275Y neuraminidase (NA) variant (BC-H5N1-H275Y), both of which emerged on farms in British Columbia, Canada, during the fall 2024 outbreak. In vitro analysis assessed replication kinetics in MDCK cells, with supernatants collected at different days post-infection (p.i.) and titrated by TCID50 and qRT-PCR. Neuraminidase inhibitor (NAI) susceptibility was determined by NA inhibition assays, whereas susceptibility to baloxavir acid (BXA) was evaluated by plaque reduction assay. In vivo virulence was evaluated in BALB/c mice infected with serial 10-fold dilutions of each virus to monitor weight loss and mortality. Viral titers in lungs, brain, nose, kidney, spleen, and heart were quantified at day 4 p.i. The BC-H5N1-WT virus was susceptible to the four antivirals tested, whereas BC-H5N1-H275Y displayed resistance to oseltamivir and peramivir but remained susceptible to zanamivir and BXA. The BC-H5N1-WT exhibited significantly higher viral replication titers than BC-H5N1-H275Y at all tested time points and showed larger plaque sizes. In mice, BC-H5N1-WT was more virulent with LD50 values of 1.78 × 103 PFUs compared to 8.71 × 104 PFUs for BC-H5N1-H275Y, and produced higher viral titers in lungs and other organs. Despite the reduced fitness of the resistant H5N1 D1.1 variant, its emergence in the absence of viral selection pressure underscores the need for continued surveillance.

Source: 

Link: https://www.tandfonline.com/doi/full/10.1080/22221751.2026.2686474

____

#Cyber Military #Operations under International #Humanitarian Law: Interpreting the Concept of “Attack” and Challenges in Protecting #Civilians

 

Abstract

Background

Given the growing use of information and communication technology across many essential industries, threats associated with military operations have emerged in cyberspace, thereby resulting in various debates concerning the extent to which International Humanitarian Law (IHL) applies to such threats.

Methods

The paper adopts an analytical and inductive approach based on traditional and customary IHL provisions, as well as reports from specialized organizations. In this regard, this study explores the legal framework for these threats and assesses the applicability of the IHL provisions to operations carried out during non-international armed conflicts and those occurring outside such contexts. The study also sheds light on the different interpretations of the concept of “attack” within the context of the IHL and assesses the degree of protection afforded to civilians and their objects in light of the distinctive features of cyberspace.

Results

The paper demonstrates that even though IHL provides a fundamental framework for such operations, its application to cyber operations is constrained by structural challenges, given the specificity of its infrastructure and the uncertainty surrounding civilian digital data. These challenges impede the practical application of the principles of distinction, proportionality, and precaution.

Conclusions

The study concludes that the concept of “attack” needs to be reinterpreted considering the indirect harm inflicted on civilians resulting from cyber operations. It also manifests the need to raise the scope of legal protection encompassing fundamental civilian digital data and confirms the possibility of developing a specialized international legal framework that governs cyber operations whether through the creation of an additional protocol or a treaty specific for such operations. Finally, the study further affirms the necessity to establish a neutral international mechanism that can conduct fact-finding tasks, investigate violations, and assign liabilities so as to promote better adherence to humanitarian principles in contemporary armed conflicts.

Source: 

Link: https://f1000research.com/articles/15-919

____

Immunoinformatics-Guided Design and In Silico Evaluation of a Multi-Epitope #Vaccine Against #Influenza A #H10N5 and #H3N2 Strains Based on HA and NA Proteins

 

Abstract

Influenza A viruses H3N2 and H10N5 represent, respectively, a persistently dominant seasonal pathogen and a newly documented zoonotic threat with the latter strain variants responsible for the first confirmed human fatality in January 2024, yet no vaccine platform currently addresses co-protection against both subtypes within a unified immunogen. We report here the immunoinformatics based vaccine design and multi-layered computational validation of a 419-amino-acid multi-epitope subunit vaccine construct targeting conserved hemagglutinin (HA) and neuraminidase (NA) antigens identified through multiple sequence alignment of the avian H10N5 (A/swine/Hubei/10/2008) and H3N2 human reference strain sequences to identify viral agents undergoing mammalian adaptations. Linear B-cell, cytotoxic T lymphocyte (CTL), and helper T lymphocyte (HTL) epitopes were predicted using ABCpred, BCEpred, BepiPred 2.0, NetMHCpan 2.1, and NetMHCpan 4.0, then filtered through VaxiJen 3.0, AllerTOP v2.1, and ToxinPred to retain only antigenic, non-allergenic, non-toxic candidates. The final construct, incorporating an avian β-defensin N-terminal adjuvant with GPGPG, AAY, and EAAAK linkers, exhibited a molecular weight of 43.9 kDa, instability index of 31.15, and SOLPro solubility probability of 0.763. Tertiary structure modeling via I-TASSER and GalaxyRefine achieved 84.4% Ramachandran-favored residues. Molecular docking against TLR3 and TLR7 yielded binding free energies of −16.1 and −16.8 kcal/mol with picomolar dissociation constants. Molecular dynamics simulations confirmed complex stability over extended trajectories. Furthermore, codon optimization produced a Codon Adaptation Index of 1.0 for E. coli K12 expression. In silico immune simulation demonstrated robust activation of humoral and cellular immunity including elevated IgG1, IgM, IFN-γ, IL-2, rapid NK cell expansion, and broad B-cell clonal diversity. These findings establish a computationally validated candidate capable of providing protection against influenza in multiple host organisms, warranting experimental advancement.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.07.03.736294v1

____

Inter-population #connectivity of southern elephant #seals and the likely intra-species #transmission #pathways of high pathogenicity avian #influenza

 

Abstract

High Pathogenicity Avian Influenza (HPAI) H5N1 clade 2.3.4.4b has spread beyond birds to affect seals across the Southern Ocean and sub-Antarctic region, with southern elephant seals (Mirounga leonina) particularly devastated. The virus, likely introduced via spillover from infected migratory birds, has killed tens of thousands of adult seals and pups throughout most of their range, though Macquarie Island remains unaffected so far. We used twenty years of elephant seal movement data from the southern Indian and Pacific oceans to assess whether seal-to-seal transmission could spread HPAI H5N1 between breeding colonies, despite the vast distances separating them (Marion Island, Iles Crozet, Iles Kerguelen, and Macquarie Island). There was substantial overlap in seals' at-sea distributions during their winter post-moult trips, when seals travel for weeks at average speeds of 3.5 km/h. Two transmission pathways were examined: (1) terrestrial "stepping stone" routes, where infected seals could pass the virus between colonies during short intervals to remain infectious were feasible from Marion Island to Kerguelen but not from Kerguelen to Macquarie Island; and (2) at-sea encounters between seals, which occurred frequently enough to enable transmission. The findings suggest that once established at Macquarie Island, the virus could potentially spread further to New Zealand's sub-Antarctic islands and mainland New Zealand. While seal-to-seal transmission appears possible, we conclude this is unlikely. Nonetheless, understanding at-sea contact rates enhances knowledge of H5N1 epidemiology and demonstrates the value of combining long-term population monitoring with movement data to understand wildlife disease dynamics.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Integrated Marine Observing System, https://ror.org/010x3gp67

CNRS

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.07.07.737127v1

____

#Filovirus #Surveillance in Communities Bordering Equatorial Guinea, #Marburg #Outbreak, #Cameroon, 2023

 

Abstract

After the 2023 Equatorial Guinea Marburg virus (MARV) outbreak, surveillance of 181 persons in southern Cameroon detected MARV antibodies in 3 persons and Ebola virus antibodies in 7. Testing of 289 captured bats, including 158 Rousettus aegyptiacus bats, did not detect MARV RNA. Enhanced surveillance for regional filovirus spillover risks is warranted.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/8/26-0117_article

____

#Genomic and structural #evidence of #SARS-CoV-2 and #MERS-CoV in migratory #birds

 

Significance

Coronaviruses are regarded as highly important pathogens of birds and mammals. Herein, we obtained three almost full-length severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes and one partial Middle East respiratory syndrome coronavirus (MERS-CoV) genome in the feces of migratory birds based on meta-transcriptome and PCR amplification. We determined the affinities and the complex structures between receptor-binding domain (RBD) of the SARS-CoV-2 viral spike protein and angiotensin-converting enzyme 2 (ACE2) protein of two migratory birds, Tundra and Black swans. Moreover, pseudotyped SARS-CoV-2 variants can enter into HeLa cells expressing ACE2 proteins of these birds. Altogether, our results expand our understanding of migratory birds as potential carrier of both SARS-CoV-2 and MERS-CoV.

Abstract

Migratory birds are the natural reservoir of influenza A virus (IAV), but their role as a carrier of SARS-CoV-2 remains unclear. Here, we report the identification of three almost full-length viral genome sequences of SARS-CoV-2 variants of concern (VOCs) in Tundra swans. These sequences are named hCoV-19/Tundra swan/Jiangxi/IMCAS_M1/2021 (IMCAS_M1), hCoV-19/Tundra swan/Jiangxi /IMCAS_M2/2021 (IMCAS_M2), and hCoV-19/Tundra swan/Jiangxi/IMCAS_M3/2021 (IMCAS_M3). IMCAS_M1 and IMCAS_M3 have the same mutations as the Beta VOC (K417N, E484K, and N501Y) in the receptor-binding domain (RBD) of the viral spike (S) protein, whereas IMCAS_M2 shares the same mutations as the Gamma VOC (K417T, E484K, and N501Y) in the RBD with all three showing their distinct mutations in the genomes. Virus receptor angiotensin-converting enzyme 2 (ACE2) proteins from both Tundra swan (tsACE2) and Black swan (bsACE2) can bind to the RBDs of all three viruses and the Alpha VOC, but not to RBD of the prototype (PT) virus. The polar contacts and hydrophobic interactions revealed by cryo-electron microscopy (cryo-EM) structures of the RBD–ACE2 complex, play key roles in virus–receptor engagement. Furthermore, HeLa cells expressing bsACE2 and tsACE2 proteins could be transduced by pseudotyped SARS-CoV-2 variants (Alpha, Beta, and Gamma) but not PT SARS-CoV-2. In addition, we obtained one partial genome of MERS-CoV named Bar-headed goose/Tibet/IMCAS_M4/2022 (IMCAS_M4) with 20,180 bp (~70.0% coverage). Our findings highlight the importance of migratory birds as potential carrier of both SARS-CoV-2 and MERS-CoV, thereby posing potential threat to public health.

Source: 

Link: https://www.pnas.org/doi/abs/10.1073/pnas.2400023123?af=R

____

Evaluation of a proposed #link between the #SARS-CoV-2 #furin #cleavage site and mouse-adapted #MERS-coronavirus MA30

 

Significance

This study formally evaluates a hypothesis that has been advanced by some scientists and public commentators in support of a nonnatural origin of SARS-CoV-2. The hypothesis proposes that the unique polybasic furin cleavage motif of SARS-CoV-2 may be technically or evolutionarily derived from a mouse-adapted laboratory strain of MERS-coronavirus (MA30). While the World Health Organization’s Scientific Advisory Group on the Origins of Novel Pathogens (SAGO) concluded that the available evidence was insufficient to support the proposed link, the underlying scientific rationale for this conclusion has not been published. We systematically assessed the evidence from genomic surveillance and conducted additional experimental studies. Together, these data do not support an evolutionary or genetic relationship.

Abstract

The origin of the polybasic furin cleavage site (FCS) of SARS-CoV-2 remains a central question in debates on the emergence of COVID-19. One hypothesis proposes a genetic relationship between the SARS-CoV-2 S1/S2 motif RRAR and the RRVR sequence found in the mouse-adapted MERS-CoV strain MERS-MA30. Here, we combined large-scale bioinformatic analysis with experimental virology to evaluate this scenario. Analysis of over 17 million SARS-CoV-2 genomes revealed that the S:684V substitution corresponding to RRVR occurred repeatedly but only sporadically, never became phylogenetically basal, and showed limited geographic and temporal spread. Using reverse genetics, we generated SARS-CoV-2 variants encoding RRVR and demonstrated that S:684V consistently reduced viral entry efficiency and competitive fitness in multiple cell systems, including human respiratory epithelial cultures. RRVR variants did not evolve toward RRAR but instead accumulated alternative substitutions. These findings do not support an evolutionary relationship between MERS-MA30 and the SARS-CoV-2 FCS.

Source: 

Link: https://www.pnas.org/doi/abs/10.1073/pnas.2601806123?af=R

____

First #Ecuadorian #Pediatric Case of Multisystem and #Neurological Involvement Associated with #Influenza A #H5N1 Virus—Case Report

 

Abstract

Influenza A (H5N1) is a highly pathogenic zoonotic virus with a human fatality rate of approximately 60%. Pediatric cases and associated neurological manifestations remain poorly documented in Latin America. This report describes the first confirmed Ecuadorian pediatric case of H5N1-associated encephalitis and multisystem organ failure in a previously healthy 9-year-old female following direct contact with infected poultry. The clinical course was characterized by an atypical initial presentation of bilateral periorbital edema and headache, progressing to acute encephalitis, cerebral ischemia, flaccid tetraplegia, central diabetes insipidus, and refractory septic shock. Diagnostic confirmation was achieved via nasopharyngeal RT-PCR, with additional RT-PCR and sequencing performed on cerebrospinal fluid, which identified conserved influenza A M1/M2 gene fragments, while laboratory markers—including marked elevations in IL-6, ferritin, and CRP—indicated a severe hyperinflammatory state. Management involved an intensive multidisciplinary approach utilizing oseltamivir, intravenous immunoglobulin, modulated-dose corticosteroids, desmopressin, and mechanical ventilation. Despite a severe clinical course, the patient achieved a favorable recovery, with a Glasgow Coma Scale score of 15/15 at discharge and only partial residual paresis and left hypoacusia as sequelae. This landmark case provides rare evidence of H5N1 neuroinvasion in a pediatric patient and demonstrates that timely detection combined with aggressive immunotherapy and antiviral treatment can improve survival. Furthermore, it underscores the critical necessity for strengthened regional molecular surveillance and clinical training to recognize atypical presentations of emerging zoonoses in Latin America, especially in cases involving contact with sick poultry.

Source: 

Link: https://www.mdpi.com/1999-4915/18/7/749

____