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Enhanced #genome #replication activity of pandemic #H1N1 #influenza A virus through PA #mutations

  ABSTRACT The 2009 pandemic H1N1 (pH1N1) influenza A virus (IAV) is a reassortant virus with two polymerase components, PA and PB2, originating from avian IAV . Avian IAV polymerase does not function efficiently in mammalian cells without host-adaptive mutations . The mechanism by which pH1N1 replicates in human hosts is not fully elucidated , as pH1N1 does not contain the host-adaptive PB2 E627K mutation required for species-specific interaction with ANP32 , which facilitates replicase (polymerase oligomer) formation. Our previous research revealed that mutations in PA played a key role in mammalian host adaptation of pH1N1. These mutations were found in two separate domains of PA, the C-terminal (CTD) and N-terminal domains (NTD). We reported that the NTD mutations increase the expression of NP through enhanced association of GRSF1 with the mRNA transcripts. However, the role of CTD mutations, which are located at the interface of the polymerase oligomers , has not been elucidat...

#Influenza D Virus in Black #Donkeys, Northern #China

  Abstract Influenza D virus (IDV) is prevalent in cattle in China , and a risk for spillover to other species exists. We detected IDV antibodies in 6/315 of black donkeys in northern China , suggesting cattle-to-donkey transmission and demonstrating the expanding host range of IDV and the need for reassessment of cross-species transmission risks. Source:  Link:  https://wwwnc.cdc.gov/eid/article/31/12/25-0666_article ____

Highly Pathogenic Avian #Influenza #H5N1 Clade 2.3.4.4b Virus #Infection in Poultry Farm #Workers, #Washington, #USA, 2024

  Abstract Poultry workers in Washington, USA, were infected with highly pathogenic avian influenza A(H5N1) virus and recovered. The viruses were clade 2.3.4.4b genotype D1.1, closely related to viruses causing poultry outbreaks . Continued surveillance and testing for influenza A(H5) clade 2.3.4.4b viruses remain essential for risk assessment and pandemic preparedness of zoonotic influenza viruses. Source:  Link:  https://wwwnc.cdc.gov/eid/article/31/12/25-1118_article ____

#Zoonotic and #Avian #Pathogen Detections in Fecal and Sediment #Samples - A Low-risk, High-throughput One Health Approach to #Surveillance

  Abstract Many pathogens, both those with human spillover potential as well as avian-specific viruses, are maintained in wild bird populations . While much surveillance for influenza A viruses (IAVs) is performed annually, surveillance for other pathogens is limited. Sampling of wild birds is often time-consuming , labour-intensive, involves physically handling wild birds, often limited in sample size, and involves handling of potentially infected birds , posing an increased risk of direct exposure for personnel. Given this, additional methods for surveillance are needed. Longitudinal, bi-weekly fecal and sediment sampling was performed at various sites in southern Manitoba, Canada , particularly focused in Winnipeg from May - October 2025. Sites were chosen based on the suitability of the area for waterfowl habitat , the presence of waterfowl in the area, as well as sites in proximity to reported outbreaks of H5N1 influenza virus . Fecal and sediment samples were collected and sc...

The spatial and temporal #spread of highly pathogenic avian #influenza in North #America: Newton's Cradle hypothesis

  Abstract The recent emergence of highly pathogenic H5N1- especially clade 2.3.4.4b has led to widespread mortality in poultry and wild birds and has raised significant concerns for the dairy industry and human health. Migratory waterfowl are considered the main source of infection, and we used publicly available surveillance data and bird observation data from continental North America to show clear seasonal signals correlated with waterfowl movement, both on the continental scale and in three of the four flyways . In early 2024, the virus expanded its host range , and we observed a phase transition with the loss of the seasonal signal coupled with a concomitant increase in the proportion of mammalian cases . We also identified a second harmonic , with a regional east-to-west movement with infections spreading between regional flyways , followed by local viral amplification. We likened this to the movement of balls in a Newton's Cradle with an analogy between potential and viral ...

Digest: #Reassortment-based #evolution of #H1N1 subtype Swine #Influenza Virus in #China

  Abstract In a new study, Zhao et al. (2025) obtain 959 whole genome sequences of H1N1 subtype swine influenza virus (SIV) isolated from China . Their analysis of the sequences , isolated between 1977 and 2020, reveals how H1N1 lineages have co-evolved and contributed to instances of zoonotic transmission within the region. This study’s findings characterize the long-term evolutionary effects of frequent viral reassortment in SIV and highlight its potential to drive future pandemics. Source:  Link:  https://academic.oup.com/evolut/advance-article/doi/10.1093/evolut/qpaf262/8400336 ____

#Remdesivir as a potent #antiviral against prototype and current #epidemic #Oropouche virus #strains (BeAn19991 and PE-IAM4637)

  Highlights •  We generated a recombinant reporter OROV that expresses the eGFP fluorescent protein in infected cells. •  We found that remdesivir efficiently inhibited the replication of Oropouche virus (OROV) using this reporter OROV. •  We demonstrated strain-dependent differences in the replication efficiency of OROV. Abstract The Oropouche virus (OROV), an orthobunyavirus transmitted by biting midges, is the causative agent of Oropouche fever , which has caused multiple outbreaks in South and Central America . During the most recent epidemic in 2023–2025, more than 25,000 laboratory-confirmed cases were reported in Brazil , and no licensed antivirals have been reported to be effective date. In this study, we generated a recombinant OROV-expressing enhanced green fluorescent protein (rOROV/GFP) to facilitate rapid and sensitive antiviral evaluation . Growth kinetics demonstrated that rOROV/GFP replicated less efficiently than wild-type rOROV and that the histori...

#Influenza PA #Substitutions and Genetic Diversity of #H1N1pdm09, #H3N2, and B/Victoria Viruses in #Japan During the 2023–2024 Season

  Abstract We characterized influenza A(H1N1)pdm09, A(H3N2), and B/Victoria viruses circulating in Japan during 2023–2024 , focusing on lineage placement relative to WHO-recommended vaccine strains and on baloxavir resistance (PA/I38T substitutions). We enrolled 210 outpatients with influenza-like illness across eight clinics in six prefectures (October 2023–September 2024). Of these, 209 had an analyzable pre-treatment respiratory specimen for RT-PCR; hemagglutinin (HA) and neuraminidase (NA) genes were sequenced by next-generation sequencing (NGS). PA/I38T substitutions that confer baloxavir resistance were assessed by cycling-probe RT-PCR, Sanger sequencing, and NGS. HA phylogenies were constructed with global datasets and WHO vaccine reference strains. Of 209 pre-treatment specimens, 181 were influenza-positive (A(H1N1)pdm09 44.2%, A(H3N2) 37.6%, B/Victoria 18.2%); 51 follow-up specimens were collected ≈4–5 days after baloxavir or neuraminidase inhibitor therapy . HA phylogeny ...

#mRNA-lipid nanoparticle #vaccines provide protection against lethal #Nipah virus #infection

  Abstract Nipah virus (NiV) is a zoonotic pathogen that causes severe encephalitis and respiratory disease in humans and multiple mammalian species. However, no licensed vaccines or therapeutics are currently available against NiV infection. In this study, we developed three mRNA vaccine candidates using a lipid nanoparticle (LNP) delivery platform : mRNA-F-LNP, comprising mRNA encoding the fusion protein (F); mRNA-G-LNP, containing mRNA encoding the attachment glycoprotein (G); and mRNA-GF-LNP, in which mRNAs encoding both F and G proteins were co-encapsulated at a 1:1 molar ratio. All three mRNA-LNPs induced robust and sustained immune responses in both mice and Syrian hamsters . Sera from immunized Syrian hamster showed high levels of cross-neutralizing antibodies against both NiV-Malaysia (NiV-M) and NiV-Bangladesh (NiV-B) strains. Notably, all three mRNA-LNPs conferred complete protection against a lethal challenge with NiV-M in Syrian hamsters. These findings demonstrate tha...

Effectiveness of #nirmatrelvir/ritonavir and #molnupiravir in reducing the #risk of short-term and long-term #cardiovascular complications of #COVID19: a target trial emulation study

  Abstract While treatment with nirmatrelvir/ritonavir or molnupiravir is effective in lowering the rate of severe COVID-19 , the effectiveness of these antivirals in reducing the risk of cardiovascular outcomes, especially among the hospitalized population, remains largely unknown . In this study, we assessed the real-world effectiveness of nirmatrelvir/ritonavir and molnupiravir on short- and long-term cardiovascular complications of COVID-19 using a target trial emulation design. Two target trials of COVID-19 antivirals were emulated by using a territory-wide, population-based, retrospective cohort of hospitalized patients in Hong Kong . Nine cardiovascular outcomes were evaluated in both short-term (day 0–21) and long-term (day 22–365) post-SARS-CoV-2 infection. Compared with the control group , the use of nirmatrelvir/ritonavir was associated with a significantly lower one-year risk of cardiovascular mortality , composite cardiovascular complications, major adverse cardiac eve...

#Serological evidence of concurrent #Lassa virus and #SARS-CoV-2 #exposure in #Ghana- a cross-sectional study

  Abstract Background The COVID-19 pandemic has exposed vulnerabilities in infectious disease surveillance , especially in West Africa where endemic viruses including Lassa fever persist. The overlapping clinical symptoms of these two infections create diagnostic challenges and the possibility of undetected co-infections. Methods A retrospective cross-sectional study was conducted using archived serum samples from a nationwide SARS-CoV-2 seroprevalence survey in Ghana . 434 samples across six regions were tested for SARS-CoV-2 total antibodies (IgG/IgM) using the WANTAI ELISA kit and Lassa virus IgG using ReLASV Pan-Lassa-NP-IgG ELISA. Results SARS-CoV-2 antibody prevalence was 64.29% (n = 279) and Lassa virus IgG prevalence was 20.28% (n = 88). Of the cohort of subjects who were seropositive for SARS-CoV-2, 20.79% were also seropositive for LASV IgG . Multivariate analysis revealed household size as a strong risk factor of dual exposure . Individuals from medium-sized households (...

#Coronavirus Disease Research #References (by AMEDEO, Dec. 21 '25)

  Infect Control Hosp Epidemiol LI Q, Novosad S, Rha B, Hua H, et al Trends of bloodstream infection incidence rates among patients on outpatient hemodialysis, National Healthcare Safety Network, 2012-2021. Infect Control Hosp Epidemiol. 2025 Dec 18:1-7. doi: 10.1017/ice.2025. PubMed           Abstract available Int J Infect Dis CHOI WS, Kim KH, Kim DS, Lee SH, et al Increased 30-day Mortality Risk in Coronavirus Disease 2019 Compared to Seasonal Influenza. Int J Infect Dis. 2025 Dec 17:108312. doi: 10.1016/j.ijid.2025.108312. PubMed           Abstract available RODGERS MA, Averhoff F, Berg MG, Anderson M, et al Robust mission-driven responses to infectious disease threats delivered by the Abbott pandemic defense coalition. Int J Infect Dis. 2026;162:108162. PubMed           Abstract available J Med Virol WU Y, Yang C, Wei X, Xiao T, et al Albendazole Suppresses S...

#Influenza and Other Respiratory Viruses Research #References (by AMEDEO, Dec. 21 '25)

  Antimicrob Agents Chemother LEONARD VHJ, Vidales DB, Taft BR, Hesse MJ, et al Identification and characterization of a novel inhibitor of influenza A virus that acts by blocking nucleoprotein oligomerization. Antimicrob Agents Chemother. 2025 Dec 19:e0114925. doi: 10.1128/aac.01149. PubMed           Abstract available Arch Virol BEDAIR NM, Sakr MA, Mourad A, Eissa N, et al Genetic characterization of highly pathogenic avian influenza A/H5N8 virus isolated from commercial poultry farms in Egypt reveals zoonotic potential. Arch Virol. 2025;171:29. PubMed           Abstract available Biochemistry WESTMAN H, Hammarstrom P, Nystrom S SARS-CoV-2 Spike Protein Amyloid Fibrils Impair Fibrin Formation and Fibrinolysis. Biochemistry. 2025;64:4818-4829. PubMed           Abstract available Epidemiol Infect STADHOUDERS L, Hoogteijling EM, Duijts L, Lebon A, et al Trends in a...

Emergence of #mammalian-adaptive #PB2 #mutations enhances #polymerase activity and #pathogenicity of #cattle-derived #H5N1 #influenza A virus

  Abstract Highly pathogenic avian influenza H5N1 poses an increasing public health risk, particularly following its spillover into dairy cows and associated human infections in the U.S. since March 2024. Here, we systematically identified critical PB2 mutations emerged during avian-to-cattle transmission and subsequent adaptation in cattle , notably PB2 M631L, which conferred pathogenicity in mice comparable to the well-characterized PB2 E627K mutation . Retrospective analysis reveals that PB2 631L also circulated in avian and human H5N1 strains during the 2013–2014 outbreaks in Cambodia and Vietnam . Additional adaptive mutations include established markers ( E627K, Q591R, D701N ), and novel variants ( I647V, G685R, K736R ). These mutations enhance polymerase activity by improving the utilization of both bovine and human ANP32A proteins , thereby increasing viral fitness and pathogenicity in mammals . The convergence of these adaptations highlights the elevated zoonotic risk of c...

#Replication and #Transmission of #Influenza A Virus in Farmed #Mink

  Abstract Farmed mink are frequently exposed to circulating influenza A viruses (IAVs), as confirmed by viral isolation and serological evidence. Previous work reveals that naïve mink serve as susceptible hosts for both avian and human influenza strains , highlighting their potential role in influenza ecology . In this study, we investigated whether farmed mink naturally pre-exposed to H9 retain the capacity to serve as “mixing vessels” for reassorting human and avian IAVs. Our results demonstrate that they remain fully susceptible and permissive to infection by both avian H6N6 and human H1N1 influenza strains . Notably, efficient transmission of these viruses occurred among farmed mink, confirming their potential to sustain viral exchange . These findings indicate that farmed mink represent highly permissive hosts capable of facilitating reassortment between circulating human and avian IAVs. Given this risk, current mink farming practices may substantially increase the likelihood...

#Cats infected with #H5N1 avian #influenza – a new infectious disease in #Poland

  Abstract Avian influenza virus (AIV) infections in cats are a new and not fully understood  problem  in Poland . These infections have drawn the attention of both veterinarians  and human medical  practitioners , mainly because of their zoonotic  potential , i.e. possible spreading to humans and  other mammals . In wild felids as  well as in domestic cats , AIV can cause severe infections , often  ending in death.  Highly pathogenic avian influenza virus (HPAIV) and low pathogenic avian  influenza virus (LPAIV) have been identified, with the recent H5N1 (2.3.4.4b  clade) outbreak  affecting poultry, wild birds and carnivores .  Transmission likely occurs through contact with  infected birds , their excretions or  contaminated raw poultry , while cat-to-cat transmission  remains unconfirmed .  First reported in Thailand in 2003, H5N1 infections in cats have since  occurred in  multiple c...

#Genetic characterization of highly pathogenic avian #influenza #H5N8 virus isolated from commercial #poultry #farms in #Egypt reveals zoonotic potential

  Abstract Highly pathogenic avian influenza (HPAI) H5N8 virus, first identified in late 2016 in Egypt, continues to circulate and has replaced the previously dominant HPAI H5N1 virus of clade 2.2.1. In this study, HPAI H5N8 was detected on 23 commercial poultry farms in Egypt . Complete genome sequences of three isolates collected in 2021 were obtained using next-generation sequencing (NGS) and subjected to genetic characterization. Phylogenetic analysis showed these isolates to belong to clade 2.3.4.4b, comprising two genotypes: EA-2021-Q and EA-2020-A . Molecular analysis of the haemagglutinin (HA) protein revealed the presence of T156A and V538A substitutions in the duck isolate and an N183S substitution in the chicken isolate . Several additional nonsynonymous mutations were identified, including 147I and 504V in the PB2 protein , 127V, 672L, and 550L in the PA protein , 64F and 69P in the M2 protein , and 42S in the NS1 protein . Comparative analysis of HA antigenic sites bet...

Highly Pathogenic Avian #Influenza: #Tracking the #Progression from IAV #H5N1 to IAV #H7N9 and Preparing for Emerging Challenges

  Abstract Highly Pathogenic Avian Influenza (HPAI) viruses, particularly IAV (H5N1), continue to pose a major global threat due to their widespread circulation and high mortality rates in birds. Management of HPAI is complicated by challenges in conserving migratory bird populations, sustaining poultry production, and uncertainties in disease dynamics. Structured decision-making frameworks , such as those based on the PrOACT model, are recommended to improve outbreak response and guide critical actions , especially when HPAI virus (HPAIV) detections occur in sensitive areas like wildlife refuges . Surveillance data from late 2024 to early 2025 show persistent HPAI activity , with 743 detections across 22 European countries and beyond, and notable outbreaks in poultry in nations like Hungary, Iceland, and the UK . The proximity of poultry farms to water sources increases environmental contamination risks. Meanwhile, HPAI A(IAV (H5N1)) and other H5Nx viruses have been detected in a ...

A #pandemic #toolbox for clade 2.3.4.4b #H5N1 #influenza virus #risk #assessment

  {Excerpt} Since 1997, more than 1000 cases of highly pathogenic avian influenza A(H5N1) have been reported in humans . During this time, A(H5N1) viruses have evolved into dozens of clades , showing ever-expanding phylogenetic diversification and geographical spread . Over the past 5 years, clade 2.3.4.4b A(H5N1) viruses have exhibited rapid global expansion in migratory birds, with spillover to an increasing range of marine and terrestrial mammalian species . Among these species are dairy cattle , not previously recognised as a permissive host for influenza A viruses (IAV), leading to widespread clade 2.3.4.4b A(H5N1) outbreaks in herds in the USA and sporadic human infections linked with exposure to infected animals since March 2024. While person-to-person transmission has not been detected in the USA, the increased geographical distribution of and susceptibility of mammalian hosts to clade 2.3.4.4b A(H5N1) viruses has brought to the forefront a need to assess the pandemic risk ...

Attachment and #replication of clade 2.3.4.4b #influenza #H5N1 viruses in #human respiratory #epithelium: an in-vitro study

  Summary Background Highly pathogenic avian influenza H5N1 viruses of the A/Goose/Guangdong/1/1996 lineage pose a global threat to wildlife, domestic animals, and humans . Cross-species transmission events to mammals, including humans , in the past 4 years highlight this threat. For influenza A viruses, crucial determinants of cross-species and intraspecies transmission to and among mammals include attachment to and replication in respiratory airway epithelial cells . Although these determinants have been studied for H5N1 viruses in the past, limited studies for clade 2.3.4.4b viruses exist. Therefore, the aim of this study was to determine the ability of recent clade 2.3.4.4b H5N1 viruses to attach to human respiratory tissues, to replicate in human airway epithelial cells and the associated immune response. Methods In this in-vitro study, we investigated three H5N1 clade 2.3.4.4b viruses (H5N1Gull2022, H5N1Polecat2022, and H5N1Bovine2024) in comparison with previously studied 2....