ETIDIOH - NEW

Abstract Prior to the discovery of bat influenza A virus (IAV) subtypes H17N10 and H18N11 , all IAVs were thought to bind sialic acid residues via hemagglutinin (HA) to mediate attachment and subsequent viral entry. However, H17 and H18 engage a proteinaceous receptor : the major histocompatibility complex class II (MHCII). The mechanistic details of this hitherto unknown protein-mediated entry are not understood. Given that conventional IAVs rely on multivalent binding to sialylated glycans , we hypothesized that bat HA similarly interacts with multiple MHCII molecules. Using photoactivated localization microscopy (PALM) on fixed and live cells, we demonstrate that bat IAV particles attach to pre-existing MHCII clusters and induce a further increase in cluster size upon binding. To measure the impact of viral attachment on the dynamics of MHCII, we employ an “inverse attachment” approach, immobilizing viral particles on coverslips before seeding live MHCII-expressing cells on top. Sin...

Abstract During infection, individual virions trigger specific cellular signaling at the virus-cell interface , a nanoscale region of the plasma membrane in direct contact with the virus. However, virus-induced receptor recruitment and cellular activation are transient processes that occur within minutes at the nanoscale. Hence, the temporal and spatial kinetics of such early events often remain poorly understood due to technical limitations. To address this challenge, we develop a protocol to covalently immobilize labelled influenza A viruses on glass surfaces before exposing them to live epithelial cells . Our method extends the observation time for virus-plasma membrane association while minimizing viral modifications, facilitating live imaging of virus-cell interactions . Using single-molecule super-resolution microscopy, we investigate virus-receptor interaction showing that viral receptors exhibit reduced mobility at the virus-binding site, which leads to a specific local recepto...

Abstract Since 2020, large-scale outbreaks of highly pathogenic avian influenza (HPAI) H5N1 in Great Britain have resulted in substantial poultry mortality and economic losses. Alongside the costs, the risk of circulation leading to a viral reassortment that causes zoonotic spillover raises additional concerns. However, the precise mechanisms driving transmission between poultry premises and the impact of potential control measures in Great Britain, such as vaccination, are not fully understood. We have developed a spatial transmission model for the spread of HPAI in poultry premises calibrated to infected premises data for the 2022--23 season using Markov chain Monte Carlo . Our results indicate that enhanced biosecurity measures and/or vaccination of the premises surrounding an identified infected premises can substantially reduce the overall number of infected premises. Our findings highlight that enhanced control measures could limit the future impact of HPAI on the poultry industr...

{Excerpt} Time Period: April 13, 2025 - April 19, 2025 -- H5 Detection :  4 sites ( 1.0% ) -- No Detection :  406 sites ( 99.0% ) -- No samples in last week :  153 sites (...) Source: US Centers for Disease Control and Prevention,  https://www.cdc.gov/bird-flu/h5-monitoring/index.html?cove-tab=0 ____

A poultry farm in Quang Tri province. Source: WOAH,  https://wahis.woah.org/#/in-review/6440 ____

Abstract Highly pathogenic H5Nx influenza A viruses are causing unprecedented, season-independent outbreaks across avian and mammalian species, including dairy cattle, a novel reservoir. The sialoside-binding properties of influenza A hemagglutinin (HA) are strongly related to its ability to infect and transmit between hosts. Mucin-like O-glycans , omnipresent in respiratory tracts, have been understudied as viral receptors due to their complexity. To address this, we synthesized 25 O-linked glycans with diverse sialosides, including modifications by fucosides and sulfates. Our findings reveal that H5Nx 2.3.4.4b viruses uniquely bind core 3 sialyl-Lewisx and Sia-Gal-β3GalNAc, glycans not recognized by classical H5 or other avian viruses. By determining its crystal structure, we resolved the structural features of both structures in an H5 hemagglutinin (HA) from a 2016 2.3.4.4b virus. While these viruses do not bind human-type receptors , their promiscuous receptor specificity enhances ...

Editor’s summary High-pathogenicity avian influenza subtype H5N1 is now present throughout the US , and possibly beyond. More cattle infections elevate the risk of the virus evolving the capacity to transmit between humans , potentially with high fatality rates . Nguyen et al. show that from a single transmission event from a wild bird to dairy cattle in December 2023, there has been cattle-to-poultry, cattle-to-peridomestic bird , and cattle-to-other mammal transmission. The movement of asymptomatic dairy cattle has facilitated the rapid dissemination of H5N1 from Texas across the US . Evolution within cattle, assessed using deep-sequencing data, has detected low-frequency sequence variants that had previously been associated with mammalian adaptation and transmission efficiency. —Caroline Ash Structured Abstract INTRODUCTION Highly pathogenic avian influenza (HPAI) viruses have critical consequences for animal health and the agricultural economy—and may have pandemic potential. HPAI ...

ABSTRACT Avian influenza is one of the major threats to poultry and human health in northern Benin , while mixed-species farming systems increase the risks of viral transmission. The present study estimated the seroprevalence of avian influenza subtypes H9N2 and H5 in indigenous chickens and guinea fowls in the Atacora and Donga regions. A total of 300 birds including 191 indigenous chickens and 109 guinea fowls, from six districts were sampled through a cross-sectional survey using systematic random sampling. Hemagglutination inhibition assay was used to detect antibodies, revealing an overall H9N2 seroprevalence of 41%, with 17.5% of samples testing positive for H5 . The seroprevalence of H9N2 was notably higher in guinea fowls (51.81% in Atacora and 52% in Donga) compared to chickens (34.95% in Atacora and 34.83% in Donga). H5 antibodies were found only in guinea fowls in Atacora (46.66%). The study also found that farms with both chickens and guinea fowls had a significantly higher...

Abstract In 2018, a clinical trial of four investigational therapies for Ebola virus disease (EVD), known as the PALM trial , was conducted in the Democratic Republic of Congo . All patients received either the antiviral remdesivir (RDV) or a monoclonal antibody product : ZMapp, mAb114 (Ebanga), or REGN-EB3 (Inmazeb). The study concluded that both mAb114 and REGN-EB3 were superior to ZMapp and RDV in reducing mortality from EVD. However, the data suggested that some patients in the RDV and ZMapp groups might have been sicker at the time of treatment initiation. Here, we assessed the efficacy of each of these therapies in a uniformly lethal rhesus monkey model of EVD when treatment was initiated 5 days after Ebola exposure. Treatment with RDV, mAb114, REGN-EB3, and ZMapp each resulted in similar survival (approximately 40% ). Survival was associated with circulating viral load at treatment initiation. A trend of more escape mutants in the GP1 and GP2 domains was observed for the mAb114 ...

Abstract H5Nx clade 2.3.4.4b high-pathogenicity avian influenza viruses (HPAIVs) have decimated wild bird and poultry populations globally since the autumn of 2020. In the United Kingdom (UK) and in continental Europe , the H5N8 subtype predominated during the first epizootic wave of 2020/21, with few detections of H5N1 . However, during the second (2021/22) and third (2022/23) epizootic waves , H5N1 was the dominant subtype. The rapid shift in dominance from H5N8 to H5N1 was likely driven by a combination of virological, immunological, and/or host-related factors . In this study, we compared viral fitness and immunological responses in ducks , a key reservoir species, using dominant genotypes of H5N1 (genotype AB) and H5N8 (genotype A) from the second wave. While viral shedding dynamics were similar for both viruses, H5N8 was more pathogenic . Antigenic analysis of post-infection duck sera revealed that the haemagglutinin (HA) protein was antigenically similar across clade 2.3.4.4b H5...

Abstract Background Baloxavir marboxil (baloxavir) rapidly reduces influenza virus shedding , which suggests that it may reduce transmission. Studies of treatment with neuraminidase inhibitors have not shown sufficient evidence that they prevent transmission to contacts. Methods We conducted a multicountry, phase 3b trial to assess the efficacy of single-dose baloxavir treatment to reduce influenza transmission from index patients to household contacts. Influenza-positive index patients 5 to 64 years of age were randomly assigned in a 1:1 ratio to receive baloxavir or placebo within 48 hours after symptom onset. The primary end point was transmission of influenza virus from an index patient to a household contact by day 5. The first secondary end point was transmission of influenza virus by day 5 that resulted in symptoms. Results Overall, 1457 index patients and 2681 household contacts were enrolled across the 2019–2024 influenza seasons; 726 index patients were assigned to the baloxa...

Abstract Colorectal cancer incidence rates vary geographically and have changed over time1 . Notably, in the past two decades, the incidence of early-onset colorectal cancer , affecting individuals under the age of 50 years, has doubled in many countries2-5. The reasons for this increase are unknown . Here, we investigate whether mutational processes contribute to geographic and age-related differences by examining 981 colorectal cancer genomes from 11 countries . No major differences were found in microsatellite unstable cancers, but variations in mutation burden and signatures were observed in the 802 microsatellite-stable cases. Multiple signatures, most with unknown etiologies , exhibited varying prevalence in Argentina, Brazil, Colombia, Russia , and Thailand , indicating geographically diverse levels of mutagenic exposure. Signatures SBS88 and ID18, caused by the bacteria-produced mutagen colibactin 6,7, had higher mutation loads in countries with higher colorectal cancer inciden...

{Excerpt} The Centre for Health Protection (CHP) of the Department of Health today (April 23) received a report of a case of severe paediatric COVID-19 and human metapneumovirus (hMPV) infection and reminded the public to observe personal, hand and environmental hygiene at all times. High-risk individuals should receive a COVID-19 vaccination as soon as possible and receive booster doses at appropriate times to minimise the risk of serious complications and death after infection. The case involves an eight-month-old girl with good past health, who developed a fever and runny nose since April 19 and sought medical attention from a private doctor the next day. She developed cough and shortness of breath on April 21 and sought medical attention from another private doctor. She attended the Accident and Emergency Department of Hong Kong Adventist Hospital – Tsuen Wan on April 22 and was transferred to the Paediatric Intensive Care Unit of Princess Margaret Hospital for treatment on the sam...

Abstract The ecological factors that led to the 1918 influenza pandemic remain unknown. We hypothesise that horses acted as intermediate hosts spreading a pre-pandemic avian-origin virus before 1918. This is supported by reports describing a large epizootic of unusually severe equine influenza beginning in 1915. Furthermore, the high horse demand during WWI resulted in one of the biggest equine mobilisations in North America between 1914 and 1918. This extensive movement of horses provided abundant opportunities for virus reassortment between pre-pandemic avian and human influenza viruses. Archived equine tissues or serum samples will be needed to test this hypothesis. Source: Journal of Infectious Diseases,  https://academic.oup.com/jid/advance-article-abstract/doi/10.1093/infdis/jiaf197/8115353?redirectedFrom=fulltext&login=false ____

ABSTRACT The highly pathogenic avian influenza virus A(H5N1) clade 2.3.4.4b has caused a human outbreak in North America since March 2024. Here, we conducted a serosurveillance study to determine the risk of A(H5N1) clade 2.3.4.4b (2024 cattle H5N1) to general population. In the initial screening of 180 serum specimens encompassing all age groups, 2.2% (4/180) had detectable neutralizing antibody (nAb) titers against reverse genetics-derived 2024 cattle H5N1, with all collected from older adults aged ≥60 years old. Further screening showed that 4.2% (19/450) of adults aged ≥60 years old had detectable nAb titers against the 2024 cattle H5N1 . 80% (4/5) serum specimens with nAb titer of ≥40 had detectable HI titer, and there was a positive correlation between nAb titer and HA binding (r = 0.3325, 95% confidence interval 0.2477 to 0.4123; P < 0.0001). The nAb titer against seasonal H1N1 virus was 4.2-fold higher for ≥60 years old individuals with detectable H5N1 nAb titer than those ≥...

Abstract We detected influenza D virus in multiple swine herds in Northern Ireland . Whole-genome sequencing showed several circulating genotypes and novel mutations in the receptor-binding site and esterase domains of the hemagglutinin-esterase fusion protein. Transmission routes of influenza D virus to swine remain to be clarified but could be direct or indirect. Source: US Centers for Disease Control and Prevention,  https://wwwnc.cdc.gov/eid/article/31/5/24-1948_article ____

Abstract Several concurrent mpox outbreaks are ongoing in the Democratic Republic of the Congo . We report a case of severe clade Ia mpox in an adult woman with indeterminate HIV status who died 16 days after symptom onset. She self-identified as a sex worker and had spent time in the capital city, Kinshasa. Source: US Centers for Disease Control and Prevention,  https://wwwnc.cdc.gov/eid/article/31/5/24-1690_article ____

Abstract The introduction and subsequent detection of highly pathogenic avian influenza (HPAI) in poultry is influenced by the virus replication fitness, transmission fitness, and virulence in poultry. These viral fitness parameters are important for implementing surveillance and control measures for poultry. This study investigates the potential application of an avian in vitro model using primary chicken embryo (CEF) and duck embryo fibroblasts (DEF) to identify the viral fitness for a reference panel of eight dominant HPAI clade 2.3.4.4 virus genotypes : four H5N1 viruses isolated between 2021 and 2024, as well as three H5N8 and one H5N6 virus isolated between 2014 and 2020. Infectious virus titre and cytopathogenicity were measured in the primary cell cultures over time and these data were analysed using a mathematical model which delineates cell populations into susceptible, latent, infectious, and dead compartments. In addition to obtaining traditional virological parameters such...

Abstract We performed serologic surveillance for selected arthropod-borne viruses (arboviruses) in bats and opossums in the Lacandona Rainforest, Chiapas, Mexico , in 2023–2024. Sera were collected from 94 bats of at least 15 species and 43 opossums of three species. The sera were assayed by the plaque reduction neutralization test (PRNT) for antibodies to eight orthoflaviviruses ( dengue viruses 1–4, St. Louis encephalitis virus , T’Ho virus, West Nile virus, and Zika virus ) and one alphavirus (chikungunya virus; CHIKV). Twelve (12.8%) bats and 15 (34.9%) opossums contained orthoflavivirus-specific antibodies . One bat (a Jamaican fruit bat) was seropositive for Zika virus , and 11 bats contained antibodies to an undetermined orthoflavivirus , as did the 15 opossums. All bats and most opossums seropositive for an undetermined orthoflavivirus had low PRNT titers, possibly because they had been infected with another (perhaps unrecognized) orthoflavivirus not included in the PRNTs. Anti...

Abstract Lassa mammarenavirus (LASV), a member of the family Arenaviridae , is a highly pathogenic virus capable of causing severe systemic infections in humans . The primary host reservoir is the Natal multimammate mouse (Mastomys natalensis), with human infections typically occurring through mucosal exposure to virus-containing aerosols from rodent excretions . To better understand the molecular mechanisms underlying LASV replication in the respiratory tract, we utilized differentiated primary human airway epithelial cells (HAECs) grown under air–liquid interface conditions, closely mimicking the bronchial epithelium in vivo. Our findings demonstrate that HAECs are permissive to LASV infection and support productive virus replication . While LASV entry into polarized HAECs occurred through both apical and basolateral surfaces , progeny virus particles were predominantly released from the apical surface , consistent with an intrinsic apical localization of the envelope glycoprotein GP...