Skip to main content

Posts

My New Space

The #ORF6 accessory #protein contributes to #SARS-CoV-2 #virulence and pathogenicity in the naturally susceptible #feline model of infection

  ABSTRACT In this study, the infection dynamics, replication, and pathogenicity of a recombinant virus containing a deletion of ORF6 (rWA1ΔORF6) on the backbone of the highly virulent SARS-CoV-2 WA1 virus (rWA1) were investigated and compared to the parental rWA1 virus. While both rWA1 and rWA1ΔORF6 viruses replicated efficiently in cultured cells , the rWA1ΔORF6 virus produced smaller plaques, suggesting reduced cell-to-cell spread. Luciferase reporter assays revealed immune-suppressing effects of ORF6 on interferon (IFN) and nuclear factor kappa B (NF-κB) signaling pathways. Pathogenesis assessment in cats revealed that animals inoculated with rWA1 were lethargic and presented with fever on days 2 and 4 post-infection (pi), whereas rWA1ΔORF6-inoculated animals developed subclinical infection . Additionally, animals inoculated with rWA1ΔORF6 presented reduced infectious virus shedding in nasal and oral secretions and broncho-alveolar lavage fluid when compared with the rWA1-inocu...
Recent posts

#USA, #Wastewater Data for Avian #Influenza #H5 (#CDC, Feb. 27 '26)

  {Excerpt} Time Period: February 15, 2026 - February 21, 2026 -- H5 Detection :  4 site(s) ( 0.8% ) -- No Detection :  495 site(s) ( 99.2% ) -- No samples in last week :  110 site(s) (...) Source: US CDC,  https://www.cdc.gov/ Link:  https://www.cdc.gov/nwss/rv/wwd-h5.html ____

#Bosnia and Herzegovina - High pathogenicity avian #influenza viruses (Inf. with) (#poultry) - Follow up report 1

  Note 27/02/2026: the number of dead animals in this outbreak was lowered after the country provided additional information. Source:  Link:  https://wahis.woah.org/#/in-review/7309 ____

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

  This is a farm with broiler parents, housed in 3 barns. Clinical signs of increased mortality and severely depressed general condition were observed. Euthanization is in progress. A protection zone (3 km) and a surveillance zone (10 km) have been put in place around the infected farm and all other restrictions and necessary measures according to Regulation (EU) 2016/429 and EU DR 2020/687 are applied. Source: WOAH. Link:  https://wahis.woah.org/#/in-review/7313 ____

Evolutionary #lineage and #host origin influence #virulence and #mammalian adaptation of #H7N9 avian #influenza viruses

  Abstract The H7N9 avian influenza virus (AIV) has posed a major global public health concern since its first detection in China in 2013 . Transmitted among wild birds and poultry , this virus has crossed the species barrier to infect humans , causing severe respiratory disease and high mortality . Although the widespread use of H7 vaccines has markedly reduced human infections , the ongoing circulation and adaptive evolution of the virus in poultry remain a serious threat . In this study, we analyzed three highly pathogenic H7N9 isolates collected in China in 2022, representing two hemagglutinin (HA) gene evolutionary lineages : Group.y.2.3 (isolate 229-4, chicken origin; isolate 782-2, quail origin) and Group.y.2.4 (isolate 621, quail origin). Pathogenicity was compared through phylogenetic analysis , molecular characterization, and infection experiments in both avian and mammalian models . Group.y.2.3 isolates displayed stronger replication and pathogenicity in chickens and mic...

#Zanamivir - #Amantadine Conjugate: A Dual-Action Agent with Broad-Spectrum Synergistic #Antiviral Efficacy

  Abstract Influenza A virus is a highly contagious respiratory pathogen, and its rapid and continuous adaptive mutations for immune escape have limited the efficacy of existing vaccines and antiviral drugs. Here, we report a multimechanism anti-influenza platform based on the conjugation of zanamivir (ZMV) with amantadine (Aman). Aman acts as a hydrophobic tag that promotes the degradation of neuraminidase and concurrently enhances the physicochemical properties of ZMV , leading to improved membrane permeability and a significantly prolonged half-life. Meanwhile, the ZMV moiety counteracts Aman-induced cytotoxic autophagy . The resulting conjugate, compound 7j , exhibits potent activity against a wide range of neuraminidase and M2 ion channel mutations . Notably, a single intravenous dose of 7j fully protected mice from a lethal H1N1 challenge . Our work demonstrates that the rational fusion of ZMV and Aman achieves synergistic multimechanistic antiviral activity with enhanced eff...

#Synergy between HA #cleavage site #sequence and NA-mediated #plasminogen recruitment as a virulence mechanism for low-pathogenic avian #influenza

  ABSTRACT An outbreak of H3N1 low-pathogenic avian influenza virus (LPAIV) in Belgium in 2019 caused unexpected levels of mortality and morbidity in poultry . These viruses possess an NA polymorphism associated with plasminogen (PLG) binding , as well as an atypical sequence around the HA cleavage site ; accordingly, HA cleavage mediated by NA-driven PLG recruitment has been proposed to underlie their systemic spread and pathogenicity. To test this, we established a reverse genetics system for A/chicken/Belgium/460/2019 and created single mutations in HA (K345R) and NA (S122N) that restored the viruses to normal consensus, as well as an HA/NA double mutant. Confirming previous work, trypsin-independent spread and HA cleavage of wild-type Ck/Belgium were observed in the presence of fetal bovine serum containing PLG in vitro. Dose-dependent HA cleavage and trypsin-independent spread were also observed in the presence of purified chicken PLG . Compared to the wild-type virus, both HA...

#Tecovirimat for the Treatment of #Mpox

  Abstract Background Tecovirimat is approved for smallpox treatment under the Food and Drug Administration Animal Rule on the basis of efficacy in nonhuman primate models of mpox (previously known as monkeypox). However, the clinical efficacy of tecovirimat against human clade II mpox is unclear . Methods In a phase 3, international, double-blind, randomized, placebo-controlled trial, we evaluated the efficacy of oral tecovirimat in adults with laboratory-confirmed clade II mpox. Participants were randomly assigned in a 2:1 ratio to receive tecovirimat or placebo for 14 days. The primary outcome was clinical resolution, assessed in a time-to-event analysis in participants with active skin or mucosal lesions. Secondary outcomes included reduction in pain, assessed in all participants with laboratory-confirmed mpox and in those with severe pain at baseline (pain score, 7 to 10; scale, 0 [no pain] to 10 [worst pain imaginable]); complete lesion healing (assessed in a time-to-event an...

#Wastewater #Surveillance for #SARS-CoV-2 in Rural #Kentucky, 2021–2023

  Abstract Wastewater testing for SARS-CoV-2 provided useful public health information during the COVID-19 pandemic yet was underutilized in rural communities . We addressed this gap by implementing wastewater surveillance and assessing its performance in 10 communities in Eastern Kentucky . We collected wastewater samples 1–2 times weekly at 10 wastewater treatment plants (WWTPs) from May 2021 until April 2023 and measured SARS-CoV-2 RNA concentrations using polymerase chain reaction testing . We calculated time-lagged correlations between wastewater concentrations and county-level reported COVID-19 cases by site. We developed a generalized linear model to estimate COVID-19 incidence from wastewater SARS-CoV-2 concentrations. The 10 participating WWTPs served 2430 to 35,575 customers , and 90% were in rural counties. We cumulatively analyzed 818 wastewater samples . Correlations between wastewater SARS-CoV-2 concentrations and COVID-19 cases were significant at seven of the WWTPs ...

Re-infection with #SARS-CoV-2 is associated with increased #antibody breadth and potency against diverse #sarbecovirus strains

  ABSTRACT The ease with which emerging SARS-CoV-2 variants escape neutralizing antibodies limits the protection afforded by a prior exposure , be it infection or vaccination. While rare, broadly neutralizing antibodies with activity toward diverse sarbecoviruses have been detected in convalescent serum . Motivated by findings that plasma responses show increased neutralization breadth and potency with continued antigen exposure , we isolated monoclonal antibodies (mAbs) after a SARS-CoV-2 re-infection and compared them to those isolated 1 year prior, after the first breakthrough infection. Among clonal lineage members identified at both time points, mAbs from the later time point showed improved neutralization potency and breadth . One mAb isolated after re-infection, C68.490, targets a conserved region in the receptor binding domain and shows remarkable activity not only against SARS-CoV-2 variants, but also diverse sarbecoviruses from more distant clades present in animal reserv...

#Mpox Multi-country external #situation #report no. 63, published 24 February 2026 (#WHO, summary)

  Highlights     • Transmission of mpox continues in sexual networks , affecting both women and men , and in some historically endemic areas .  - All clades of monkeypox virus (MPXV) continue to circulate.  - Unless mpox outbreaks are rapidly contained and human-to-human transmission is interrupted , there is a risk of sustained community transmission .  • In January 2026, 50 countries across all WHO regions reported a total of 1334 new confirmed mpox cases , including three deaths (case fatality ratio [CFR] 0.2%).  - Of these cases , 66% were reported in the African Region.  • Four regions observed a decline in confirmed cases in January, compared to December 2025, while the European Region reported an increase in confirmed cases. • Twenty countries in Africa reported active transmission of mpox in the last six weeks (5 January – 15 February 2026), with 1142 confirmed cases, including four deaths (CFR 0.4%).  - Countries reporting the highes...

#Argentina - #Influenza A #H5 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

  {A Coscoroba Swan. By Charles J. Sharp - Own work, from Sharp Photography, sharpphotography.co.uk, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=179069673 } ___ {A Black-Necked Swan. By Charles J. Sharp - Own work, from Sharp Photography, sharpphotography.co.uk, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=178158764 } ___ {A Fulvous Whistling Duck. By JeffreyGammon - Own work, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=158156460 } ___ {A Brown-Hooded Gull. By Charles J. Sharp - Own work, from Sharp Photography, sharpphotography.co.uk, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=179073441 } ____ Contact with wild migratory birds present in the area is presumed to be the likely source of infection. Virological analysis has identified the presence of the H5 subtype of high pathogenicity avian influenza (HPAI). The determination of the neuraminidase subtype is pending in order to complete the chara...

#Argentina - High pathogenicity avian #influenza #H5 viruses (Inf. with) (#poultry) - Immediate notification

  At a heavy breeding poultry farm located in the province of Buenos Aires , an increase in mortality and the presence of clinical signs consistent with high pathogenicity avian influenza (HPAI) were observed. Given the clinical suspicion, official intervention was carried out, including a health inspection and the collection of diagnostic samples for processing. Laboratory analyses confirmed a positive result for high pathogenicity avian influenza subtype H5 (HPAI H5). The event occured on a farm raising heavy breeding stock. On 21/02/2026, the National Service of Agri-Food Health and Quality (SENASA) received a notification concerning mortality and clinical signs consistent with high pathogenicity avian influenza (HPAI) which began on 19/02/2026, as reported by the reporting person. On 22/02/2026, the suspicion was officially addressed with the restriction of the establishment and taking of samples for official diagnosis. On 23/02/2026, the samples tested positive for HPAI H5. Al...

#Report on #influenza viruses received and tested by the #Melbourne #WHO CC for #Reference and Research on #Influenza during 2024

  Abstract As part of its role in the World Health Organization (WHO) Global Influenza Surveillance and Response System (GISRS), the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne received 12,180 human influenza-positive samples during 2024 . Viruses were analysed for their antigenic, genetic, and antiviral susceptibility properties . Selected viruses were propagated in qualified cells or embryonated hens’ eggs for potential use in seasonal influenza virus vaccines. During 2024 , influenza A( H1N1 )pdm09 and A( H3N2 ) viruses predominated , accounting for 33% and 42%, respectively, of all viruses received, compared to 5% for influenza B/Victoria . Of note, one influenza A(H5N1) virus was also received in 2024 . The majority of A(H1N1)pdm09 (98%), A(H3N2) (88%) and influenza B (100%) viruses analysed at the Centre were found to be antigenically and genetically similar to the respective WHO recommended vaccine strains for the Southern Hemisphere in 2024...

Longitudinal #assessment of functional #antibodies to a novel #influenza virus strain across age groups

  Abstract Newly emerging influenza virus strains pose a constant threat as they encounter a population lacking neutralizing antibodies against the new strain . However, cross-reactive non-neutralizing antibodies (nnABs) may be present and assist in mitigating disease symptoms via various effector mechanisms, including antibody-dependent cellular cytotoxicity (ADCC). Although nnABs to influenza virus have received more attention lately , little information is available on their age-related prevalence , steady-state levels, functional properties , and changes in these parameters over time. Using longitudinal samples from adolescents, adults, and older adults , collected before and after the 2009 swine flu pandemic , we comprehensively characterized the specificity and functionality of nnAB responses against H1N1 pandemic 2009 (H1N1pdm09) virus . Remarkably, all participants exhibited cross-reactive antibodies to this virus before having encountered it through infection or vaccinatio...

Evaluating #primer and #probe #mismatch tolerance in an #Influenza A #matrix gene RT #qPCR using contemporary human and zoonotic strains

  Abstract Background :  Genetic drift and host-associated adaptation in influenza A viruses threaten the long-term reliability of RT-qPCR-based diagnostics , particularly when nucleotide mismatches arise within primer and probe binding regions . Conventional assay evaluations often emphasize sequence conservation but rarely assess functional mismatch tolerance across divergent subtypes and hosts.  Methods :  We performed an in silico evaluation of a matrix (M) gene–targeted RT-qPCR assay by aligning primer and probe binding regions against 22 H1N1 isolates and representative H3N2 and H5N1 reference strains, including recent zoonotic isolates from avian and bovine hosts . Nucleotide mismatches were identified, quantified, and mapped relative to assay components and oligonucleotide termini. Mismatch burden was summarized by subtype and assay region.  Results :  H1N1 isolates exhibited complete conservation across primer and probe regions. In contrast, H3N2 a...

Primary bovine embryonic #fibroblasts demonstrate variable #fitness following #infection with avian influenza #H5N1 strains and are susceptible to a recently circulating human #H1N1pdm09 strain

  ABSTRACT The recent emergence of highly pathogenic avian influenza (HPAI) H5N1 (clade 2.3.4.4b, genotype B3.13) in dairy cattle presents substantial challenges to the agricultural sector and public health. Mechanistic studies of infection and transmission in cattle have proven difficult due to animal handling restrictions and the limited availability of established cell culture models. Primary bovine embryonic fibroblasts (BeEFs) were isolated and investigated here as a model to study influenza A virus (IAV) infection dynamics. We compared sialylation profiles , infectious virus production, viral replication, and plaque morphology in BeEFs following infection with the bovine HPAI H5N1 and an earlier 2.3.4.4b genotype (B1.1) isolated in 2022. The data presented here demonstrate increased expression of α-2,3 sialic acids compared to α-2,6 sialic acids in BeEFs , similar to sialylation profiles previously reported in bovine mammary tissue . These data also display increased viral fi...

#SARS-CoV-2 Error Catastrophe Under #Molnupiravir: #Mutagenic Enhancement Enables Viral #Persistence with Impaired Fitness

  Abstract Molnupiravir induces mutations that render severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication-competent through error catastrophe mechanisms . Previous studies showed no resistant virus emergence during prolonged molnupiravir treatment, with no resistant variants reported . However, these approaches were limited by genetic uniformity at passage initiation. To investigate viral population dynamics under enhanced genetic diversity, we employed mutagenic pre-treatment using 5-fluorouracil (5-FU) and favipiravir to generate diverse quasi-species populations before molnupiravir selection pressure. Viral populations were treated with stepwise increasing molnupiravir concentrations (10 μM ⟶ 25 μM ⟶ 40 μM) over ten serial passages . Viral detectability, plaque morphology, and mutation accumulation were analyzed using molecular and sequencing approaches . Only high-concentration favipiravir (1000 μM) pre-treatment maintained detectable viral RNA through ten ...

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

{Coscoroba Swan. By Charles J. Sharp - Own work, from Sharp Photography, sharpphotography.co.uk, CC BY-SA 4.0,  https://commons.wikimedia.org/w/index.php?curid=179069673 } ___ On February 19, 2026, park rangers from the National System of Protected Areas (SNAP) reported observing two birds of the same species displaying neurological signs . They were able to access one of the animals, which subsequently died. The carcass was properly preserved and sent to the official laboratory for analysis. The emergency protocol was immediately activated. An area of 5 kilometres around the point of detection was defined. There are no commercial poultry farms within the area under analysis. The Official Veterinary Services of the departments of Maldonado and Rocha are visiting establishments in the area. The survey consists of identifying the establishment and owner; georeferencing; confirming the presence of birds (chickens/multiple species); evaluating management conditions and the existen...

The #bovine mammary #gland as a crucible for zoonotic #influenza virus emergence: Receptor-mediated #adaptation of HPAI #H5N1 clade 2.3.4.4b

  Abstract The recent emergence of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b in U.S. dairy cattle marks a pivotal shift in the ecology of influenza A viruses (IAVs), signaling an unexpected expansion into a major livestock species . This review explores the molecular mechanisms underpinning this cross-species transmission , focusing on the unique sialic acid receptor landscape of the bovine mammary gland as a critical determinant. We synthesize emerging evidence that this tissue, which co-expresses both avian-type (α2,3-linked) and human-type (α2,6-linked) sialic acid receptors , functions as a novel biological crucible for viral adaptation . Within this environment, H5N1 virus faces selective pressure for hemagglutinin (HA) mutations —such as Q226L and N193D—that can alter receptor binding specificity toward human-like glycans , potentially bridging the species barrier. Recent studies confirm that bovine H5N1 virus isolates exhibit dual receptor-binding avidity ...