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Context and significance Wang et al. provided valuable insights into the epidemiological patterns of avian influenza virus (AIV) spillover and the role of H9N2 in the process. Their analysis highlighted the significant contribution of the internal genes (INGEs) from 12 key strains of H9N2 in facilitating human adaptability by reducing the species barrier between poultry and humans , essentially acting as internal genetic donors for AIV spillover . Due to its low pathogenicity, H9N2 has been neglected in poultry vaccination programs , leading to a lack of vaccines specifically targeting the INGEs of these 12 key strains. Their findings suggest that reducing the prevalence of H9N2 is fundamental to mitigating AIV spillover risks. Highlights •  H9N2 exerts a promoting effect on the spillover of avian influenza viruses (AIVs) •  Expansion of AIV spatial and host ranges reveals an emerging risk of its spillover •  Prevalence of AIVs in human -contacted hosts reveals a re-emerg...

ABSTRACT The H5N1 avian panzootic has resulted in cross-species transmission to birds and mammals, causing outbreaks in wildlife, poultry, and US dairy cattle with a range of host-dependent pathogenic outcomes . Although no human-to-human transmission has been observed, the rising number of zoonotic human cases creates opportunities for adaptive mutation or reassortment . This Gem explores the history, evolution, virology, and epidemiology of clade 2.3.4.4b H5N1 relative to its pandemic potential. Pandemic risk reduction measures are urgently required. Source: Journal of Virology,  https://journals.asm.org/doi/full/10.1128/jvi.02209-24?af=R ____

Abstract Highly pathogenic avian influenza A(H5N1) virus has caused a multistate outbreak among US dairy cattle , spreading across 16 states and infecting hundreds of herds since its onset. We rapidly developed and optimized PCR-based detection assays and sequencing protocols to support H5N1 molecular surveillance . Using 214 retail milk samples from 20 states for methods development, we found that H5N1 virus concentrations by digital PCR strongly correlated with quantitative PCR cycle threshold values ; digital PCR exhibited greater sensitivity. Metagenomic sequencing after hybrid selection was best for higher concentration samples, whereas amplicon sequencing performed best for lower concentrations. By establishing these methods, we were able to support the creation of a statewide surveillance program to perform monthly testing of bulk milk samples from all dairy cattle farms in Massachusetts , USA, which remain negative to date. The methods, workflow, and recommendations described p...

Abstract The coronavirus membrane protein (M) is the main organizer of coronavirus assembly. Here, we report on an M-targeting molecule , CIM-834, that blocks the assembly of SARS-CoV-2. CIM-834 was obtained through high-throughput phenotypic antiviral screening followed by medicinal-chemistry efforts and target elucidation. CIM-834 inhibits the replication of SARS-CoV-2 (including a broad panel of variants) and SARS-CoV. In SCID mice and Syrian hamsters intranasally infected with SARS-CoV-2, oral treatment reduced lung viral titres to nearly undetectable levels, even (as shown in mice) when treatment was delayed until 24 h before the end point. Treatment of infected hamsters prevented transmission to untreated sentinels. Transmission electron microscopy studies show that virion assembly is completely absent in cells treated with CIM-834. Single-particle cryo-electron microscopy reveals that CIM-834 binds and stabilizes the M protein in its short form, thereby preventing the conformati...

ABSTRACT Unexpected outbreaks caused by the H5N1 highly pathogenic avian influenza virus (HPAIV) in dairy cows in the United States (US) have raised significant veterinary and public health concerns . When and how the H5N1 HPAIV was introduced into dairy cows and the broader epidemiology of influenza A virus (IAV) infections in cattle in the US remain unclear. Herein, we performed a retrospective study to screen more than 1,700 cattle serum samples collected from different bovine breeds in the US from January 2023 to May 2024 using an enzyme-linked immunosorbent assay (ELISA) targeting the nucleoprotein (NP) to detect IAV infections, and the positive samples were further tested by hemagglutination inhibition (HI) assay . Results showed that 586 of 1,724 samples (33.99%) from 15 US states were seropositive by the NP ELISA assay , including 78 samples collected in 2024 and 508 samples collected in 2023 . Moreover, the HI assay revealed that 45 of these ELISA-positive samples were positiv...

LETTER Transmission among mammals of bovine highly pathogenic avian influenza (HPAI) H5N1 viruses , which have caused outbreaks in US dairy cattle (1–3), has been demonstrated in ferrets by our group (4, 5) and the US Centers for Disease Control and Prevention (CDC) (6). These studies showed that these viruses can be transmitted among ferrets via respiratory droplets , albeit with lower efficiency than seasonal human influenza viruses. In contrast, bovine HPAI H5N1 viruses spread easily among ferrets through direct contact (3 of 3 [100%] ferrets) (6). Although ferrets are frequently used for influenza virus transmission (7–9) and vaccine efficacy (10, 11) studies, they demand considerable housing space and personnel and can be difficult to handle. Here, we investigated the transmissibility of the bovine HPAI H5N1 virus A/Texas/37/2024 (TX/37), which was 100% lethal in ferrets inoculated with as little as 10 plaque-forming units (PFUs) (5) by using a hamster model .  (...) Bovine HP...

Abstract In the past two decades, two pandemic respiratory viruses (H1N1 and SARS-CoV-2) have emerged via spillover from animal reservoirs . In an effort to avert future pandemics, surveillance studies aimed at identifying zoonotic viruses at high risk of spilling over into humans act to monitor the `viral chatter' at the animal-human interface . These studies are hampered, however, by the diversity of zoonotic viruses and the limited tools available to assess pandemic risk. Methods currently in use include the characterization of candidate viruses using in vitro laboratory assays and experimental transmission studies in animal models . However, transmission experiments yield relatively low-resolution outputs that are not immediately translatable to projections of viral dynamics at the level of a host population. To address this gap, we present an analytical framework to extend the use of measurements from experimental transmission studies to generate more quantitative risk assessm...

Abstract The ongoing panzootic of highly pathogenic avian influenza (HPAI) H5 clade 2.3.4.4b has caused widespread poultry mortality and raised concerns about zoonotic pandemics and wildlife conservation . France recently adopted a preventive vaccination strategy , vaccinating domestic ducks with inactivated and mRNA vaccines . This study evaluates the impact of this campaign on reducing HPAI H5 outbreaks. Using predictive modeling based on previous outbreak data, the expected number of outbreaks in 2023-24 without vaccination was significantly higher than the observed cases, indicating a 95.9% reduction attributable to vaccination . These findings suggest that vaccination effectively mitigated the HPAI H5 outbreak in France. Source: BioRxIV,  https://www.biorxiv.org/content/10.1101/2024.08.28.609837v3 ____

Abstract Ebola virus (EBOV) and Marburg virus (MARV) are zoonotic filoviruses that cause hemorrhagic fever in humans . Correlative data implicate bats as natural EBOV hosts , but neither a full-length genome nor an EBOV isolate has been found in any bats sampled. Here, we model filovirus infection in the Jamaican fruit bat (JFB), Artibeus jamaicensis, by inoculation with either EBOV or MARV through a combination of oral, intranasal, and subcutaneous routes . Infection with EBOV results in systemic virus replication and oral shedding of infectious virus. MARV replication is transient and does not shed. In vitro, JFB cells replicate EBOV more efficiently than MARV, and MARV infection induces innate antiviral responses that EBOV efficiently suppresses. Experiments using VSV pseudoparticles or replicating VSV expressing the EBOV or MARV glycoprotein demonstrate an advantage for EBOV entry and replication early , respectively, in JFB cells. Overall, this study describes filovirus species-sp...

Highlights The current review highlights the following major findings from the literature. 1.The genomic control of pathogenic properties of murine β-coronavirus. 2.Plausible mechanism of virus-induced neuroinflammatory demyelination and axonal loss. 3.Spike protein as a major determinant of MHV-induced neuropathogenesis. 4.The minimal essential motif in fusion peptide responsible for neuropathogenesis. 5.mCoV research sheds light on hCoV neuropathogenesis and helps design anti-virals. Abstract Coronaviruses have emerged as a significant challenge to human health . While earlier outbreaks of coronaviruses such as SARS-CoV and MERS-CoV posed serious threats , the recent SARS-CoV-2 pandemic has heightened interest in coronavirus research due to its pulmonary pathology , in addition to its neurological manifestations . In addition, the patients who have recovered from SARS-CoV-2 infection show long-term symptoms such as anosmia, brain fog and long COVID. A major hurdle in studying these v...

  Ann Intern Med Correction: Anticoagulation Among Patients Hospitalized for COVID-19. Ann Intern Med. 2025 Mar 18. doi: 10.7326/ANNALS-25-00916. PubMed          Antiviral Res SAFIRIYU AA, Hussain A, Dewangan N, Kasle G, et al The fusion peptide of the spike protein S2 domain may be a mimetic analog of beta-coronaviruses and serve as a novel virus-host membrane fusion inhibitor. Antiviral Res. 2025 Mar 16:106144. doi: 10.1016/j.antiviral.2025.106144. PubMed           Abstract available XU M, Zhang Z, Sun Y, Mai H, et al Corrigendum to "IgA class switching enhances neutralizing potency against SARS-CoV-2 by increased antibody hinge flexibility" [Antiv. Res. (2025) 106082]. Antiviral Res. 2025 Mar 20:106146. doi: 10.1016/j.antiviral.2025.106146. PubMed          Graefes Arch Clin Exp Ophthalmol ZUREIK A, Couturier A, Delcourt C Evolution of ophthalmological care in adult with ...

  Am J Med HOLLAND J, Sheehan D, Brown S, O'Flanagan S, et al Immune Response and Cognitive Impairment in Post-COVID Syndrome: A Systematic Review. Am J Med. 2025;138:698-711. PubMed           Abstract available PASCULLI P, Zingaropoli MA, Dominelli F, Solimini AG, et al Insights into Long COVID: Unraveling Risk Factors, Clinical Features, Radiological Findings, Functional Sequelae and Correlations: A Retrospective Cohort Study. Am J Med. 2024 Sep 17:S0002-9343(24)00569-2. doi: 10.1016/j.amjmed.2024. PubMed           Abstract available XU J, Wu D, Yang J, Zhao Y, et al Adult Outpatients with Long COVID Infected with SARS-CoV-2 Omicron Variant. Part 1: Oral Microbiota Alterations. Am J Med. 2025;138:732-741. PubMed           Abstract available YOO KH, Lee SH, Cho Y, Kim YJ, et al Synergistic Effect of SARS-CoV-2 Infection and COVID-19 Vaccination on the Risk of Ven...

Abstract Highly pathogenic avian influenza viruses (HPAIV) of subtype H5N1 (clade 2.3.4.4b) have crossed the species barrier and caused a mastitis-like infection in dairy cows . The high levels of infectious virus found in the milk raised considerable concerns about the safety of raw milk products . This study examined the effect of temperature and pH on the stability of HPAIV and low-pathogenic avian influenza viruses (LPAIV). We found that H5N1 HPAIV remained infectious in milk at 4 degrees Celsius for four weeks , with slow decreases at 21 degrees Celsius, and complete inactivation at 37 degrees Celsius after four weeks . H5N1 LPAIV was stable at 50 degrees Celsius for 30 minutes but inactivated at higher temperatures (55 degrees Celsius for 10 minutes, 60 degrees Celsius for 1 minute, or 72 degrees Celsius for 30 seconds). At pH levels between 6 and 10 , the virus remained stable but was partially inactivated at pH 5.0 and completely inactivated at pH 4.0. During yogurt production,...

Abstract Rationale and Objectives :  Iron availability and metabolism are important in the pathogenesis of bacterial infections . More recently, links have been reported between iron and the severity of viral infections . In this study, we characterize a crucial relationship between iron metabolism and IAV infection and disease.  Methods :  Iron-related gene expression was assessed in human airway epithelial cells (AEC) infected with IAV. AECs were cultured with ferric iron, iron-loaded transferrin, or iron chelator, deferoxamine (DFO), prior to infection with IAV. Mice were placed on a high iron diet for 8 weeks prior to infection with IAV or treated with anti-transferrin receptor-1 (TFR1) antibody during IAV infection. The effects of iron modulation and depletion of TFR1-mediated responses on IAV infection were assessed.  Measurements and main results :  Iron-related gene expression and metabolism are altered systemically and in lung tissues and AECs during IA...

Abstract Objective :  To analyze the epidemiological, etiological and genetic characteristics of influenza virus in Shandong Province during 2023-2024.  Methods :  The surveillance data of influenza-like illness (ILI) in sentinel hospitals in Shandong from 2023 to 2024 were collected and analyzed. The isolated influenza strains with hemagglutination titers ≥8 were selected for antigenicity analysis , drug susceptibility test, gene sequencing and evolutionary analysis .  Results :  From 2023 to 2024, the positive rate of influenza virus in Shandong was 8.51% (23 663/277 995), the highest positive rate was in the age group of 5-14 years (15.78%, 6 073/38 478), and the highest positive rate was in the 49th week (35.86%, 2 264/6 313). Both antigenicity analysis and evolutionary analysis showed that the A(H1N1)pdm09 subtype and B(Victoria) strain had good matching effect and close evolutionary distance with the 2023-2024 surveillance year vaccine strain. The A(H3N2) ...

Abstract Infections caused by endemic viruses , and the vaccines used to control them, often provide cross-protection against related viruses. This cross-protection has the potential to alter the transmission dynamics and likelihood of emergence of novel zoonotic viruses with pandemic potential. Here, we investigate how changes in population immunity after the COVID-19 pandemic have impacted the likelihood of emergence of a novel sarbecovirus , termed SARS-CoV-X. We show that sera from patients with different COVID-19 immunological histories possess cross-neutralising antibodies against the spike (S) protein of multiple zoonotic sarbecoviruses . Mathematical simulations using these viruses show a significant reduction in their likelihood of emergence in populations with current levels of SARS-CoV-2 natural and vaccine-derived immunity, with the outcome determined by the extent of cross-protection and the R_0 of the novel virus. We also show that preventative vaccination programs agains...

Abstract A sustained outbreak of H5N1 influenza virus among wild fowl and domestic livestock has caused more than 70 zoonotic infections in humans in the United States , including one death. The Centers for Disease Control and Prevention has recommended rapid H5 subtyping for all hospitalized cases with influenza A virus infection to enable prompt initiation of antiviral treatment , as well as infection prevention and implementation of public health measures to control spread. To address these needs, we developed a multiplex RT-qPCR assay to subtype H5 influenza virus in nasal, nasopharyngeal, and conjunctival specimens with a limit of detection of 230 copies/mL. No cross-reactivity was observed with other common respiratory viruses, including seasonal H3N2 and H1N1 influenza A viruses. We retrospectively subtyped 590 influenza A-positive clinical specimens processed by University of Washington labs between March 2024 and February 2025, including 512 specimens collected during the 2024...

Abstract Introduction   In the light of the COVID-19 pandemic many countries are trying to widen their pandemic planning from its traditional focus on influenza. However, it is impossible to draw up detailed plans for every pathogen with epidemic potential. We set out to try to simplify this process by reviewing the epidemiology of a range of pathogens with pandemic potential and seeing whether they fall into groups with shared epidemiological traits.  Methods   We reviewed the epidemiological characteristics of 19 different pathogens with pandemic potential (those on the WHO priority list of pathogens, different strains of influenza and Mpox). We extracted data on the proportion of presymptomatic transmission , incubation period , serial interval and basic reproduction number (R0) for the targeted pathogens. We applied unsupervised machine learning (specifically K-means and hierarchical clustering) to categorise these pathogens based on these characteristics.  Resul...

Abstract Introduction :  Advanced outbreak analytics played a key role in governmental decision-making as the COVID-19 pandemic challenged health systems globally. This study assessed the evolution of European modelling practices , data usage, gaps, and interactions between modellers and decision-makers to inform future investments in epidemic-intelligence globally.  Methods :  We conducted a two-stage semi-quantitative survey among modellers in a large European epidemic-intelligence consortium. Responses were analysed descriptively across early, mid-, and late-pandemic phases. Policy citations in Overton were used to assess the policy impact of modelling.  Findings :  Our sample included 66 modelling contributions from 11 institutions in four European countries. COVID-19 modeling initially prioritised understanding epidemic dynamics. Evaluating non-pharmaceutical interventions and vaccination impacts became equally important in later phases. 'Traditional' surve...

Abstract Pharmacometric assessment of antiviral efficacy in acute influenza informs treatment decisions and pandemic preparedness. We assessed natural viral clearance in untreated acute influenza to guide clinical trial design. Standardized duplicate oropharyngeal swabs were collected daily over 14 days from 80 untreated low-risk Thai adults , with viral densities measured using qPCR. We evaluated three models to describe viral clearance: exponential, bi-exponential, and growth-and-decay . The growth-and-decay model provided the best fit, but the exponential decay model was the most parsimonious. The median viral clearance half-life was 10.3 hours (interquartile range [IQR]: 6.8-15.4), varying by influenza type: 9.6 hours (IQR: 6.2-13.0) for influenza A and 14.0 (IQR: 10.3-19.3) hours for influenza B. Simulated trials using clearance parameters from the exponential decay model, showed that 120 patients per arm provide over 90% power to detect treatments accelerating viral clearance by ...