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Multiple introductions of #equine #influenza virus into the #UK resulted in widespread #outbreaks and #lineage #replacement

Abstract Influenza A viruses (IAVs) are prime examples of emerging viruses in humans and animals. IAV circulation in domestic animals poses a pandemic risk as it provides new opportunities for zoonotic infections. The recent emergence of H5N1 IAV in cows and subsequent spread over multiple states within the USA, together with reports of spillover infections in humans, cats and mice highlight this issue. The horse is a domestic animal in which an avian-origin IAV lineage has been circulating for >60 years . In 2018/19, a Florida Clade 1 (FC1) virus triggered one of the largest epizootics recorded in the UK , which led to the replacement of the Equine Influenza Virus (EIV) Florida Clade 2 (FC2) lineage that had been circulating in the country since 2003. We integrated geographical, epidemiological, and virus genetic data to determine the virological and ecological factors leading to this epizootic. By combining newly-sequenced EIV complete genomes derived from UK outbreaks with existi...

4th #meeting of #IHR (2005) Emergency #Committee regarding upsurge of #mpox 2024 – Temporary #recommendations (#WHO, June 9 '25)

Fourth meeting of the International Health Regulations (2005) Emergency Committee regarding the upsurge of mpox 2024 – Temporary recommendations The Director-General of the World Health Organization (WHO), following the fourth meeting of the International Health Regulations (2005) (IHR)   Emergency Committee regarding the upsurge of mpox 2024 , held on 5 June 2025, from 12:00 to 17:00 CEST, concurs with its advice that the event continues to meet the criteria of a public health emergency of international concern and, considering the advice of the Committee, he is hereby issuing a revised set of temporary recommendations. The WHO Director-General expresses his most sincere gratitude to the Chair, Members, and Advisors of the Committee. The proceeding of the fourth meeting of the Committee will be shared with States Parties to the IHR and published in the coming days. Temporary recommendations These temporary recommendations   are issued to  States Parties   experienci...

E627V #mutation in #PB2 protein promotes the #mammalian #adaptation of novel #H10N3 avian #influenza virus

Abstract Since 2021, the novel H10N3 has caused four cases of human infection in China, the most recent of which occurred in December 2024 , posing a potential threat to public health. Our previous studies indicated that several avian H10N3 strains are highly pathogenic in mice and can be transmitted between mammals via respiratory droplets without prior adaptation. By analyzing the genome sequence , we found that these H10N3 viruses carry the PB2-E627V mutation , which is becoming increasingly common in several subtypes of avian influenza viruses (AIV); however, its mechanism in mammalian adaptation remains unclear. Using a reverse genetics system , we investigated the role of PB2-E627V in the adaptation of H10N3 to mammals and poultry. Our findings demonstrate that the PB2-E627V mutation is critical for the high pathogenicity of novel H10N3 in mice and its ability to be transmitted through the air among mammals . Additionally, we found that the role of PB2-627 V in promoting AIV adap...

Death of Actaeon, Titian (1559 - 1575)

  Public Domain. Source: WikiArt,  https://www.wikiart.org/en/titian/death-of-actaeon-1562 ____

#Coronavirus Disease Research #References (by AMEDEO, June 7 '25)

  Ann Intern Med MARCUCCI M, Chan MTV, Painter TW, Efremov S, et al Effects of a Hypotension-Avoidance Versus a Hypertension-Avoidance Strategy on Neurocognitive Outcomes After Noncardiac Surgery. Ann Intern Med. 2025 Jun 3. doi: 10.7326/ANNALS-24-02841. PubMed           Abstract available GOLDMAN JM, Moyer DV Flying the Plane While Building It: Lessons From the COVID-19 Pandemic. Ann Intern Med. 2025 Jun 3. doi: 10.7326/ANNALS-25-02436. PubMed          Antiviral Res MALUNE P, Esposito F, Tramontano E Unveiling SARS-CoV-2's heart: role, structure and inhibition of SARS-CoV-2 RNA-dependent RNA polymerase. Antiviral Res. 2025 Jun 3:106208. doi: 10.1016/j.antiviral.2025.106208. PubMed           Abstract available BMJ MURPHY F Covid-19: New variant spreading across Asia is found in UK. BMJ. 2025;389:r1161. PubMed          LOOI MK Trump wa...

#Influenza and Other Respiratory Viruses Research #References (by AMEDEO, June 7 '25)

  BMC Pediatr ALRASHED R, Almeshawi I, Alshammari A, Alhamoud W, et al Burden of bronchiolitis post-COVID-19 pandemic in children less than 2 years old in 2021-2024: experience from a tertiary center in Saudi Arabia. BMC Pediatr. 2025;25:453. PubMed           Abstract available BIGLARI HN, Ahmadi A, Alidousti K, Pouredalati M, et al Growth in the first two years in children born to mothers infected with COVID-19 during pregnancy: a cohort study. BMC Pediatr. 2025;25:448. PubMed           Abstract available CHENG J, Wu Y, Ma H, Tang M, et al C-reactive protein and serum amyloid A protein as complementary biomarkers in differentiating viral and bacterial community-acquired pneumonia in children. BMC Pediatr. 2025;25:445. PubMed           Abstract available J Gen Virol CAPELASTEGUI F, Goldhill DH H5N1 2.3.4.4b: a review of mammalian adaptations and risk of pandemic e...

History of Mass Transportation: The FS ALn 772 Autorail

  By Kabelleger / David Gubler (http://www.bahnbilder.ch) -  http://www.bahnbilder.ch/pictures/medium/8253.jpg , CC BY-SA 3.0,  https://commons.wikimedia.org/w/index.php?curid=16836731 Source: Wikipedia,  https://en.wikipedia.org/wiki/FS_Class_ALn_772 ____

Efficacy and safety of #onradivir in adults with acute uncomplicated #influenza A infection in #China ...

Summary Background Onradivir (ZSP1273) is a potent inhibitor of the PB2 subunit of influenza A virus (IAV) polymerase . Our previous, phase 2 clinical trial showed that a 600 mg regimen of onradivir initiated within 48 h of symptom onset can expedite the recovery of adult patients from acute, uncomplicated influenza. Here, we aimed to evaluate the safety and therapeutic efficacy of onradivir in a larger group with acute, uncomplicated influenza. Methods This randomised, double-blind, multicentre, placebo-controlled and oseltamivir-controlled, phase 3 trial was conducted at 68 clinical sites in China . Eligible participants were adults (aged 18–64 years) with an influenza-like illness who screened positive by rapid IAV antigen testing at the first clinical visit, and had a fever (axillary temperature ≥38·0°C) with at least one moderate systemic and one moderate respiratory symptom within 48 h of symptom onset. Patients were randomly assigned into three treatment groups, stratified by in...

#Virological characteristics of the #SARS-CoV-2 #NB181 #variant

{Excerpt} After the spread of SARS-CoV-2 JN.1, its subvariants, such as KP.3 (JN.1.11.1.3)1 and KP.3.1.1 (JN.1.11.1.3.1.1),2 and XEC (a recombinant lineage of two JN.1 subvariants),3 emerged and rapidly spread globally. Subsequently, LP.8.1 (JN.1.11.1.1.1.3.8.1),4 a descendant lineage of KP.1.1.3 (JN.1.11.1.1.1.3), accounts for approximately 30% of all global infections as of April, 2025 , as per data from Nextstrain. Thereafter, NB.1.8.1 (XDV.1.5.1.1.8.1), a descendant lineage of XDV , has started to spread worldwide. XDV is a recombinant lineage of XDE (a recombinant lineage of GW.5.1 [XBB.1.19.1.5.1] and FL.13.4 [XBB.1.9.1.13.4]) and JN.1. NB.1.8.1 has acquired seven spike substitutions and 23 non-spike substitutions compared with JN.1 (appendix pp 15–16). Compared with the XEC spike protein, the NB.1.8.1 spike bears four substitutions : G184S, K478I, A435S, and L1104V (appendix pp 15–16). We estimated the relative effective reproduction number (Re) of NB.1.8.1 using a Bayesian mult...

Enhancing protective efficacy and immunogenicity of #hemagglutinin-based #influenza #vaccine utilizing adjuvants developed by BECC

Abstract Seasonal influenza viruses continue to pose a significant threat, causing substantial morbidity and mortality in the US and worldwide despite the availability of vaccines and antivirals. These challenges may be addressed by improving vaccine immunogenicity through the inclusion of adjuvants that enhance immune responses against key antigens including influenza hemagglutinin (HA). BECC (Bacterial Enzymatic Combinatorial Chemistry) adjuvants are novel Toll-like Receptor 4 (TLR4) ligands created by modifying enzymes from lipid A synthesis pathways in Gram-negative bacteria. This study compares the ability of the biological and synthetic versions of these adjuvants to enhance the efficacy of recombinant HA (rHA) antigens in mouse influenza virus challenge . Mice immunized with rHA adjuvanted with BECCs stimulate the humoral and cell-mediated arms of the immune system without exhibiting cytotoxicity/pyrogenicity. A robust HA-specific immunoglobulin subtype, especially IgG2a, respon...

#Influenza A virus #polymerase co-opts distinct sets of host proteins for #RNA transcription or #replication

Abstract The influenza A virus polymerase, consisting of a heterotrimer of three viral proteins, carries out both transcription and replication of the viral RNA genome . These distinct activities are regulated by viral proteins that vary in abundance during infection, and by various co-opted host cell proteins, which serve as targets for the development of novel antiviral interventions . However, little is known about which host proteins direct transcription and which replication. In this report, we performed a differential interactome screen to identify host proteins co-opted as either transcription- or replication-specific factors. We found that distinct sets of host proteins interact with the influenza polymerase as it carries out the different activities. We functionally characterised HMGB2 and RUVBL2 as replication-specific cofactors and RPAP2 as a transcription-specific cofactor. Our data demonstrate that comparative proteomics can be used as a targeted approach to uncover virus-...

#USA, #Wastewater Data for Avian #Influenza A(#H5) (CDC, June 6 '25)

  {Excerpt} Time Period: May 25, 2025 - May 31, 2025 - H5 Detection :  10 sites ( 2.5% ) - No Detection :  389 sites ( 97.5% ) - No samples in last week :  52 sites (...) Source: US Centers for Disease Control and Prevention,  https://www.cdc.gov/nwss/rv/wwd-h5.html ____

#Antigenic and #virological characteristics of #SARS-CoV-2 #variants BA.3.2, #XFG, and #NB181

{Excerpt} The SARS-CoV-2 saltation variant BA.3.2 , harbouring over 50 mutations relative to its ancestral BA.3 lineage , has recently drawn global attention (figure A). Notably, BA.3.2 exhibits 44 mutations distinct from the currently dominant LP.8.1/LP.8.1.1 variant (appendix p 4), raising speculation about its potential to drive an outbreak similar to BA.2.86 /JN.1, particularly following its first detection outside South Africa in the Netherlands on April 2, 2025.1–5 A critical evaluation of its antigenic profile and infectivity is essential to establish its likelihood of prevailing. (...) Source: The Lancet Infectious Diseases,  https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00308-1/fulltext?rss=yes ____

#Serological insights into #MERS-CoV dynamics of #antibody responses during acute and convalescent phases and their clinical relevance for #diagnostics and immunity

Abstract Introduction Middle East respiratory syndrome (MERS) is a zoonotic viral respiratory disease caused by the Middle East respiratory syndrome coronavirus (MERS-CoV), associated with severe clinical outcomes and high mortality. Objectives Our study examined the kinetics of anti-MERS-CoV IgM and IgG antibodies during the acute and convalescent phases of infection, focusing on their correlations with clinical variables such as age and viral load. Methods Serum samples were collected from PCR-confirmed MERS-CoV patients (n = 23) during both phases and compared to healthy controls (n = 23) using validated ELISA-based assays. Results IgM levels peaked in the acute phase and declined significantly in the convalescent phase , while IgG levels were sustained and markedly higher during recovery . Correlation analyses revealed positive relationships between antibody levels and patient age (acute IgM: r = 0.56, p < 0.01; convalescent IgG: r = 0.59, p < 0.01) and viral loads (acute IgM...

Immediate #PB2-E627K amino acid #substitution after single #infection of highly pathogenic avian #influenza #H5N1 clade 2.3.4.4b in mice

Abstract The highly pathogenic avian influenza virus (HPAIV) H5N1 clade 2.3.4.4b has rapidly disseminated globally , with mammalian infections reported in multiple species. Recent evidence of mammal-to-mammal transmission has heightened concerns about the virus’s potential adaptation to mammals . The polymerase basic 2 (PB2) protein E627K mutation appears to be of key importance for mammalian adaptation. We isolated an HPAI H5N1 clade 2.3.4.4b virus from wild birds in Korea with 96% E and 4% K at amino acid position 627 of PB2 . To investigate the genomic characteristics of this clade regarding mammalian adaptation, we studied the replication and transmission of the H5N1 virus in mice. Two experiments with different challenge-to-contact ratios were conducted to assess transmission dynamics and mutation development . In experiment 1, a 4:1 challenge-to-contact ratio resulted in 100% transmission among direct-contact mice , with all mice succumbing to the infection. In experiment 2, a 1:...

Chimeric #hemagglutinin and #M2 #mRNA #vaccine for broad #influenza subtype protection

Abstract Since multiple and unpredicted influenza viruses cause seasonal epidemics and even high-risk pandemics , developing a universal influenza vaccine is essential to provide broad protection against various influenza subtypes. Combined with the mRNA lipid nanoparticle-encapsulated (mRNA-LNP) vaccine platform and chimeric immunogen strategy , we developed a novel cocktail mRNA vaccine encoding chimeric HAs (cH5/1-BV, cH7/3) and intact M2 (termed Fluaxe), which confers broad protection against major circulating IAVs and IBVs , as well as highly pathogenic avian influenza . Two-dose intramuscular immunization of Fluaxe in mice elicited cross-reactive neutralizing antibodies , T cell responses, and long-lived immunity, resulting in robust protection against multiple lethal influenza virus infections and severe acute lung injuries . In particular, intramuscular administration stimulated systemic immunity together with a prominent lung tropism of memory cells . Moreover, Fluaxe immuniza...