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A versatile #H5N1-VSV #platform for safe #influenza virus #research applications

  ABSTRACT The H5N1 strain of influenza A virus (IAV) continues to cause severe infections in a range of avian and mammalian species , including sporadic but concerning cases in humans. There is growing concern that circulating H5N1 strains could lead to widespread human outbreaks . Research with highly pathogenic H5N1 viruses is restricted to Biosafety Level 3 (BSL-3) laboratories. Vesicular stomatitis virus (VSV)-based vaccine vectors expressing heterologous viral proteins from Ebola, SARS-CoV-2, Lassa virus, etc., have previously been shown to be safe and effective in animal models and human clinical trials . Here, we report the development of a recombinant VSV expressing the hemagglutinin (HA) and neuraminidase (NA) genes of H5N1 IAV (H5N1-VSV), which serves as a versatile platform to study various aspects of H5N1 IAV biology. H5N1-VSV replicated robustly to titers comparable to those of the full H5N1 virus in multiple cell lines. In mice , H5N1-VSV vaccination was safe, elicit...

#Inflammatory, transcriptomic, and #cell fate responses underlying the #mammalian #transmission of avian #influenza viruses

  ABSTRACT Airborne transmissibility of avian influenza viruses (AIVs) in humans is considered an essential component of their pandemic risk . Although several viral factors regulating airborne transmission (AT) have been delineated, it is not known what, if any, responses at the respiratory epithelia are determinants of AIV AT. Using responses in the ferret nasal epithelium to a panel of H1N1 AIVs, we describe host responses that segregate with AT phenotypes . AIV infection upregulated interferon alpha and gamma responses and IL-6 JAK-STAT signaling and downregulated oxidative phosphorylation . Single-cell transcriptomics revealed that cellular genotoxic stress and NF-kB, interferon, and cell fate pathways differentiated host responses to AIVs with different transmissibilities. These responses culminated in greater AIV antigen-containing exudate and debris in the respiratory spaces of the nasal epithelium of ferrets inoculated with AT AIVs. More abundant CMPK2, SP100, and CXCL10 t...

#USA, #Wastewater Data for Avian #Influenza #H5 (#CDC, August 8 '25)

  {Summary} Time Period: July 27, 2025 - August 02, 2025 -- H5 Detection :  4 sites ( 0.9% ) -- No Detection :  430 sites (99.1%) -- No samples in last week :  24 sites (...) Source: US Centers for Disease Control and Prevention,  https://www.cdc.gov/nwss/rv/wwd-h5.html ____

#India - High pathogenicity avian #influenza #H5N1 viruses (#poultry) (Inf. with) - Immediate notification

  Two Poultry Farms in the Odisha State. Source: WOAH,  https://wahis.woah.org/#/in-review/6694 ____

Post-exposure #prophylaxis regimen of #rabies monoclonal #antibody and #vaccine in category 3 potential exposure patients ...

  Summary Background Rabies is almost invariably fatal . A rabies monoclonal antibody (RmAb) was approved in India in 2016 for passive prophylaxis. This post-marketing study aimed to evaluate the long-term safety, immunogenicity, and efficacy of a post-exposure prophylaxis (PEP) regimen containing RmAb. Methods This phase 4, open-label, randomised, active-controlled study was conducted at 15 tertiary care hospitals in India . Patients aged 2 years or older with WHO category 3 rabies exposure by a suspected rabid animal were eligible if the exposure occurred less than 72 h before enrolment, or less than 24 h before enrolment for exposures to the face, neck, hand, or fingers. Participants were randomly assigned (3:1) to receive either RmAb (Rabishield; Serum Institute of India, Pune, India) plus a purified Vero cell rabies vaccine (PVRV; Rabivax-S) or equine rabies immunoglobulin (ERIG; Equirab) plus PVRV as PEP. In each treatment group, patients were further randomly assigned (1:1) ...

#MERS-related #coronavirus circulating in #pangolins exhibits strong fusogenicity in #human #cells and high sensitivity to fusion inhibitors

Highlights •  MjHKU4r-CoV-1 with high fusogenicity induces inflammatory responses in human cells •  6-HB structure determination unveils MjHKU4r-S-mediated membrane fusion mechanism •  MjHKU4r-CoV-1 HR2 peptides exhibit potent activity by targeting viral HR1 domain •  Stapled peptide MjHKU4r-HR2P10 shows potent and broad-spectrum anti-CoV activity Summary Unlike preceding MERS-related coronaviruses, the recently identified MjHKU4r-CoV-1 strain can directly infect human cells . Nonetheless, its potential pathogenic attributes and underlying molecular mechanisms remain unclear. We find that MjHKU4r-CoV-1 induces significant inflammation , including interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α), and exhibits pronounced fusogenicity mediated by its spike (S) protein, leading to extensive syncytium formation . This suggests the possibility that MjHKU4r-CoV-1 possesses strong pathogenic potential in humans . Further, we successfully reveal the molecular mechan...

Highly conserved #Betacoronavirus #sequences are broadly recognized by #human T cells

Highlights •  Conserved T cell epitope regions elicit strong CD4+ and CD8+ T cell responses in SARS2-exposed •  CTERs enhance cross-reactivity across multiple Betacoronaviruses •  Targeting non-spike proteins expands immune breadth and HLA coverage •  Removing low population coverage regions preserves cross-reactivity Summary The COVID-19 pandemic highlighted the critical need for vaccine strategies capable of addressing emerging viral threats . Betacoronaviruses, including severe acute respiratory syndrome coronavirus ( SARS-CoV ), Middle East respiratory syndrome ( MERS ), and SARS-CoV-2 , present significant pandemic risks due to their zoonotic potential and genetic diversity . T cell-mediated immunity has demonstrated durable responses and strong cross-reactivity, offering a promising avenue for achieving broad immunity within a viral family. In this study, we combined comprehensive epitope mapping with sequence conservation analyses to identify conserved T cell ...

#Italy, #WNV and #Usutu Virus Weekly #Surveillance #Bulletin No. 4, July 7 '25: 84 new confirmed cases (ISS)

{Summary} -- Since the last update (July 31), eighty-four new confirmed cases of human infection with West Nile Virus have been reported.  -- Since the start of epidemic season, there were 173 confirmed WNV cases, of which:  - 72 were West Nile Neuroinvasive Disease (WNND): (2 in Piedmont, 2 Lombardy, 4 Veneto, 1 Friuli-Venezia Giulia, 2 Emilia-Romagna, 37 Latium, 21 Campania, 1 Basilicata, 1 Sardegna),  - 14 were asymptomatic cases in blood donors ,  - 85 were West Nile Fever cases,  - 1 was an asymptomatic case  -- Among the confirmed cases, there were eleven fatalities : 1 in Piedmont, 4 Latium, 6 .  - The case-fatality rate among WNND cases is at 15% (during 2018 season it was 20%, whereas in 2024 it was 14%).  -- No new confirmed cases of Usutu Virus human infection have been reported during current surveillance week. (...) Source: High Institute of Health,  https://www.epicentro.iss.it/westnile/bollettino/Bollettino_WND_2025_04.pdf ____...

Dynamics of endemic #virus re-emergence in #children in #USA following #COVID19 #pandemic (2022–23): a prospective, multicentre, longitudinal, immunoepidemiological surveillance study

Summary Background The Pandemic Response Repository through Microbial and Immune Surveillance and Epidemiology (PREMISE) programme was established to translate knowledge gained from global immunoepidemiological surveillance into a better understanding of population-level dynamics of emerging and re-emerging infections , as well as into the discovery and development of biomedical countermeasures against potential pandemic threats. As proof of principle for this approach, we conducted a longitudinal immunoepidemiological study in children in the USA, focusing on enterovirus D68 (EV-D68) infection dynamics but also capturing surveillance of a broad array of other endemic respiratory pathogens. Serendipitously, our sampling spanned the lifting of widespread COVID-19 non-pharmaceutical interventions (NPIs) in 2022–23, following a unique period during which virus exposure markedly diminished. Methods This prospective, multicentre, longitudinal, immunoepidemiological surveillance study enroll...

#Nipah virus #infection - #India (#WHO D.O.N., August 6 '25)

Situation at a glance Between 17 May and 12 July 2025, the Information and Public Relations Department, Government of Kerala informed through a series of official press releases about four confirmed cases , including two deaths , due to Nipah virus (NiV) infection in two districts of Kerala State.  NiV infection is a bat-borne disease transmitted to humans through infected animals (such as bats or pigs), contaminated food or, less commonly, through close contact with infected individuals.  Since 1998 NiV outbreaks have been reported in Bangladesh, India, Malaysia , the Philippines , and Singapore .  In India, NiV infections have occurred multiple times since 2001 with outbreaks in West Bengal State in 2001 and 2007, and in Kerala State regularly since 2018.  Since 2018, Kerala has reported a total of nine NiV outbreaks . While the state has a strong healthcare system and improved infection control measures since 2023, it is advisable to maintain strong preparedness a...

#Influenza and Other Respiratory Viruses Research #References (by AMEDEO, August 6 '25)

  BMJ WISE J RFK Jr bans thiomersal from influenza vaccines in "safety" move. BMJ. 2025;390:r1576. PubMed          Epidemiol Infect KELLY GE, Petti S, Noah N Excess respiratory, circulatory, neoplasm, and other mortality rates during the Covid-19 pandemic in the EU and their implications. Epidemiol Infect. 2025;153:e86. PubMed           Abstract available Eur J Epidemiol ORTQVIST AK, Soderling J, Magnus MC, Urhoj SK, et al COVID-19 infection increases the risk of venous thromboembolism during pregnancy and the postpartum period. Eur J Epidemiol. 2025;40:779-788. PubMed           Abstract available BAUMKOTTER R, Yilmaz S, Chalabi J, Ten Cate V, et al Risk tools for predicting long-term sequelae based on symptom profiles after known and undetected SARS-CoV-2 infections in the population. Eur J Epidemiol. 2025;40:789-801. PubMed         ...

#Coronavirus Disease Research #References (by AMEDEO, August 6 '25)

  Am J Respir Crit Care Med MATTHAY MA, Zhou H, Sarma A, Alipanah-Lechner N, et al Treatment with Allogenic Mesenchymal Stromal Cells for Moderate to Severe Acute Respiratory Distress Syndrome: A Double-Blind, Placebo-controlled, Multi-Center, Phase 2b Clinical Trial (STAT). Am J Respir Crit Care Med. 2025 Jul 29. doi: 10.1164/rccm.202411-2254. PubMed           Abstract available Ann Intern Med FELDMAN CH, Santacroce L, Bassett IV, Thaweethai T, et al Social Determinants of Health and Risk for Long COVID in the U.S. RECOVER-Adult Cohort. Ann Intern Med. 2025 Jul 29. doi: 10.7326/ANNALS-24-01971. PubMed           Abstract available Antiviral Res PATEL D, De R, Azadi N, Lee S, et al Discovery of broad-spectrum antivirals targeting viral proteases using in silico structural modeling and cellular analysis. Antiviral Res. 2025;241:106245. PubMed           Abstract avai...

Analysis of the metagenomic assembled #genome of #MERS-CoV and Alpha-CoV from #Camelus dromedarius in #Saudi Arabia

Abstract Background Dromedary camels are known carriers of Middle East respiratory syndrome coronavirus (MERS-CoV). This study aimed to identify respiratory RNA viruses circulating in the nasal cavities of camels that could potentially cause disease in humans. Methods Shotgun metagenomic paired-end sequencing was performed on four pools of nasal swabs collected from 40 camels originating from Sudan and Djibouti, using the MiSeq platform. Results Alphacoronavirus 229E was commonly detected in the camel pools. MERS-CoV was found in both pools from Sudan and one from Djibouti . Camel parainfluenza virus 3 (PIV3) was detected in the male camel pool from Sudan . Furthermore, near-complete (99.9 %) metagenomic assembled genomes (MAGs) of alphacoronavirus 229E (SIAU MAG01) and MERS-CoV (SIAU MAG02) were retrieved from the female camel pool from Sudan . Another MAG of alphacoronavirus 229E (SIAU MAG03) was recovered from a male camel pool imported from Sudan . In the phylogenetic analysis, SIA...

Attachment #Patterns of Avian #Influenza #H5 Clade 2.3.4.4b Virus in Respiratory Tracts of Marine #Mammals, North #Atlantic Ocean

Abstract Highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus infections have caused substantial mortality events in marine mammals in recent years. We hypothesized that the high number of infections and disease severity could be related to cell tropism in respiratory tracts . Therefore, we examined the attachment pattern of an H5N1 clade 2.3.4.4b virus (H52022) as a measure for cell tropism in the respiratory tracts of harbor seals, gray seals, harbor porpoises, and bottlenose dolphins and compared it with an H5N1 clade 2.1.3.2 virus (H52005) and a human seasonal H3N2 virus using virus histochemistry. Both H5 viruses attached abundantly to olfactory and respiratory mucosa in the upper respiratory tract of both seal species. H52022 attached more abundantly than H52005 to epithelial cells in the lower respiratory tract of all species. The observed attachment possibly explains the susceptibility of marine mammal species for recent H5N1 viruses and the observed development of se...

Identification and characterization of novel #bat #coronaviruses in #Spain

Abstract The zoonotic transmission of bat coronaviruses poses a threat to human health. However, the diversity of bat-borne coronaviruses remains poorly characterized in many geographical areas. Here, we recovered eight coronavirus genomes by performing a metagenomic analysis of fecal samples from hundreds of individual bats captured in Spain , a country with high bat diversity. Three of these genomes corresponded to potentially novel coronavirus species belonging to the alphacoronavirus genus . Phylogenetic analyses revealed that some of these viruses are closely related to coronaviruses previously described in bats from other countries, suggesting a shared viral reservoir worldwide. Using viral pseudotypes, we investigated the receptor usage of the identified viruses and found that one of them can use human ACE2 , albeit with lower affinity than SARS-CoV-2. However, the receptor usage of the other viruses remains unknown. This study broadens our understanding of coronavirus diversity...

#Ireland - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

  On 30th July 2025 HPAI H5N1 was confirmed in a young chicken in a backyard flock in Co Donegal . The bird was submitted to the Regional Veterinary Laboratory and virological testing confirmed HPAI at the CVRL. Control measures were put in place following detection on 30th July 2025. The 7 remaining birds of the backyard flock were euthanised and have tested negative for AI PCR. Further results to follow. Update: report updated to reflect the control measures applied (stamping out applied) as per the above report. Source: WOAH,  https://wahis.woah.org/#/in-review/6691 ____