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Loss of α2,3-linked #sialoside in the receptor-binding site of a #H5N1 #influenza hemagglutinin identified in a #human patient

  Abstract In November 2024, an adolescent female in British Columbia was hospitalized presenting with severe symptoms including respiratory failure due to infection with a novel H5N1 subtype influenza strain (BC24). Using cryogenic electron microscopy (cryo-EM), we show here that the N169 α2,3-linked auto-glycan that is found in the sialic acid binding site of previously studied H5 hemagglutinin (HA) proteins is absent in purified BC24 HA protein , suggesting greatly reduced affinity for α2,3-linked sialosides . Glycan microarray analysis shows that the BC24 HA protein displays reduced or no binding not just to most α2,3-linked sialosides, but also to α2,6-linked sialosides . Full-length BC24 HA expressed in A549 lung alveolar carcinoma cells drives membrane fusion, albeit at significantly lower levels than previous H5 HA proteins, and post-infection sera from the patient display strong binding to BC24 HA and HA proteins from other influenza subtypes. The high virulence of the BC2...
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Using an evolutionary #epidemiological #model of #pandemics to estimate the #infection #fatality ratio for #humans infected with avian #influenza viruses

  Abstract The risk of highly pathogenic avian influenza infection to humans is challenging to estimate because many human avian influenza virus (AIV) infections are undetected as they may be asymptomatic , symptomatic but not tested , and as contact tracing is difficult because human-to-human spread is rare. We derive equations that consider the evolutionary mechanisms that give rise to pandemics and are parameterized to be consistent with records of past pandemics. We estimate that thousands of human AIV infections occur worldwide in an average year and estimate the infection fatality ratio as 32 deaths per 10,000 infections (95% confidence interval: [9.6, 75]). We estimate that preventing 20% of animal-to-human influenza spillovers annually would delay pandemic emergence by an average of 9.4 years . There is a high level of uncertainty in our estimates due to the few records of past pandemics, but even so this infection fatality ratio is comparable to SARS-CoV-2 during the recen...

Immune history confers #antibody - and T cell-dependent cross-protection against highly pathogenic avian #influenza #H5N1 viruses

  ABSTRACT The outbreak of highly pathogenic avian H5 influenza (HPAI) clade 2.3.4.4b in cattle has spread across the United States . Mice with pre-existing immunity to H1N1 virus or with a live-attenuated influenza vaccine showed protection against a lethal bovine-derived HPAI H5N1 viral challenge . Notably, ferrets with mixed immunity also demonstrated protection against a feline-derived H5N1 virus, independent of cross-reactive neutralization titers , but antibodies to whole virus were observed. To investigate protective factors, we conducted T cell epitope mapping using published H1N1 viral sequences and found high conservation of key T cell epitopes in the bovine HPAI H5N1 strain . Depletion of T cells in mice prior to and during primary H1N1 infection impacted cross-protective antibodies to H5N1 virus, with CD4 depletion increasing mortality and CD8 depletion mildly impacting morbidity upon H5N1 viral challenge. This underscores the need to investigate memory T cell responses...

Integrating #Prevention and #Response at the Crossroads of #Henipavirus #Preparedness, Hendra@30 Conference, 2024

  Abstract Diseases caused by henipaviruses, exemplified by Hendra virus and Nipah virus, pose a serious risk to public health because of their epidemic potential and high case-fatality rates and the paucity of medical countermeasures to mitigate them. In December 2024, a group of 150 scientists from 16 countries convened in Geelong, Victoria, Australia, to mark the 30th anniversary of the discovery of Hendra virus . The Hendra@30 conference built upon its predecessor conference held in 2019 in Singapore, Nipah@20, by expanding its program across broader disciplines and integrating sessions on human sociology and disease ecology into the main scientific discussions. We describe key highlights from Hendra@30 and reflect on 4 key elements that have advanced henipavirus research and medical countermeasures research and development. We propose that integrating bat ecology into henipavirus research blueprints will enable development of ecologic countermeasures that prevent spillover and...

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

  A wild mute swan in Etelä-Suomen aluehallintovirasto Region. Source:  Link:  https://wahis.woah.org/#/in-review/7213 ____

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

A wild mute swan.  Last outbreak in wild birds in Podkarpackie region was confirmed in February 2025. Source:  Link:  https://wahis.woah.org/#/in-review/7215 ____

Detection of Avian #Influenza #H5–Specific #Antibodies by Chemiluminescent Assays

  Abstract We evaluated 2 electrochemiluminescence serologic assays to detect avian influenza H5 antibodies . Both assays identified H5 antibodies from both serum and dried blood spots and had strong specificity and minimal cross-reactivity in human and avian samples. Such assays can support populationwide serologic surveys aimed at assessing population-level immunity. Source:  Link:  https://wwwnc.cdc.gov/eid/article/32/1/25-1117_article ____

Emerging Respiratory #Virus #Threats from #Influenza D and Canine #Coronavirus HuPn-2018

  Abstract In 2009 and again in 2019, public health warnings were confirmed by the emergence, rapid widespread transmission, and lethality of novel influenza and coronaviruses . The world continues to suffer disease from these respiratory viruses. Two newly recognized emergent respiratory viruses, influenza D and canine coronavirus HuPn-2018 , have been shown to have considerable potential for causing future human epidemics , but diagnostics and surveillance for the viruses are lacking. We reviewed data regarding influenza D virus and coronavirus canine coronavirus HuPn-2018 . Those data strongly indicate that these viruses are major newly recognized threats . However, little is being done to respond to or prevent disease associated with these viruses, warranting the question of whether we will learn from previous pandemics. Source:  Link:  https://wwwnc.cdc.gov/eid/article/32/1/25-1764_article ____

#Milk as a #Transmission Vehicle for Highly Pathogenic Avian #Influenza #H5N1

Abstract Highly pathogenic avian influenza A (H5N1) (H5N1 hereafter) is an emerging pathogen in mammals . The recent recognition of H5N1 in dairy cattle increases opportunities for human exposure and infection and may accelerate a trajectory toward sustained human-to-human transmission . Furthermore, the presence of virus at high concentration in unpasteurized milk raises new risks for humans , especially infants and children . Milk has been identified as a vehicle for viral transmission in and between mammalian species, including humans. Sialic acids (SAs) found on cell surfaces are important mediators of species susceptibility to specific influenza strains and play an important role in viral tropism . New data demonstrate that SA receptors with α2,3 linkages capable of binding avian influenza strains are present in human mammary tissue . The presence of SA receptors that can bind avian influenza and a comparative analysis of viral transmission risk of raw and pasteurized milk in seve...

From #pandemic #influenza to novel #coronaviruses: emerging infectious diseases of the 21st century

  Highlights •  Global mobility, climate pressures, and ecological change drive emerging infections. •  Highly pathogenic influenza strains, including H5N1, pose ongoing spillover risks and pandemic potential. •  SARS, MERS, and COVID-19 illustrate the pandemic potential of novel coronaviruses. •  Nipah, Ebola, Pteropine orthoreovirus and Zika remain high-impact threats for global health security. •  Mass gatherings can amplify transmission risks of emerging high-consequence viruses. •  Strengthened surveillance, diagnostics, and One Health strategies are essential for pandemic preparedness. Abstract Emerging infectious diseases have risen significantly in the twenty-first century as ecological disruption, climate change, expanding human–animal interfaces , and global mobility intensify opportunities for pathogen transmission . This review synthesizes historical and contemporary evidence across viral, bacterial, fungal, and parasitic threats to charact...

#Sialic acids are a #barrier to the entry of non-influenza #orthomyxoviruses

  Abstract Sialic acids (SAs) are abundantly expressed on vertebrate cell surfaces and are widely recognized as key viral attachment factors , particularly for influenza viruses . However, their role remains understudied in other orthomyxoviruses, such as thogoto and quaranja viruses , which are tick-borne viruses sporadically infecting humans. Enzymatic removal of SAs increased the infectivity of Thogoto and Dhori viruses , as well as pseudotypes carrying the glycoproteins of Oz, Sinu, and Wellfleet Bay viruses . A similar effect on pseudotype infectivity was observed following the binding of specific lectins to SAs. These findings indicate that, in contrast to influenza viruses, SAs act as a barrier to the entry of these orthomyxoviruses . Experimental evolution of the Sinu and Wellfleet Bay virus glycoproteins revealed point mutations that partially overcame this barrier . Given the abundance of sialic acids in mucosal tissues, we speculate that SAs may contribute to the inabili...

#Management of #critical illness in an #adolescent caused by highly pathogenic avian #influenza #H5N1 virus infection in #BC, #Canada

  Summary Highly pathogenic avian influenza A(H5N1) viruses have been circulating among wild birds and are enzootic in poultry in some areas of the world with spillover to a wide range of terrestrial and marine mammals. Since 1997, sporadic animal to human , primarily poultry to human, transmission of highly pathogenic avian influenza A(H5N1) viruses has been reported in 25 countries . More recently there have been locally acquired infections in the Americas due to the 2.3.4.4b clade of the virus. Most of the recently detected human infections in the USA have been relatively mild but there have been cases of critical illness reported in several countries. In this Grand Round we present the first locally acquired highly pathogenic avian influenza A(H5N1) virus infection in Canada , which was in a 13-year-old female, who developed severe disease requiring prolonged critical care . She was infected with a clade 2.3.4.4b, genotype D1.1 virus and developed evidence of cytokine storm and...

Comprehensive evaluation of #therapeutic #effectiveness and #safety profiles of #baloxavir marboxil for managing #influenza virus infection in #pediatric populations: a systematic #review with pooled meta-analytic data

  Abstract Objective :  This systematic review aimed to assess the clinical effectiveness and safety profile of baloxavir marboxil for managing influenza in pediatric populations . Methods :  This review has been registered on the INPLASY platform (INPLASY2025110063). Designed in accordance with the PRISMA 2020 guidelines, we searched four major biomedical databases (PubMed, Embase, Web of Science, Cochrane Library) covering publications from January 1, 2015, to January 30, 2025 . Eligibility criteria encompassed both randomized controlled trials and observational cohort studies evaluating this antiviral agent in children with laboratory-confirmed influenza. Methodological rigor was appraised using the Cochrane Collaboration's risk of bias instrument for randomized controlled trials (RCTs) and the Newcastle-Ottawa Quality Assessment Scale for cohort studies. Statistical synthesis was conducted using RevMan 5.3 software (Version 5.3.5) with metafor package implementation. ...

An #mRNA #vaccine encoding the #Ebola virus glycoprotein induces high neutralizing #antibody titers and provides strong protection against lethal infections in mouse models

  Abstract Ebola virus (EBOV) is the causative agent of Ebola disease (EBOD), a viral hemorrhagic fever with a notably high case fatality rate . Current treatments for EBOD are limited to monoclonal antibodies or two licensed viral vector vaccines , a recombinant vesicular stomatitis virus (rVSV)-vectored vaccine or an adenovirus and modified vaccinia Ankara regimen. However, comparisons of protection, efficacy, and durability with alternative nucleotide platforms remain understudied . Here, we evaluated the immunogenicity of an mRNA vaccine expressing the EBOV glycoprotein (GP) in parallel with rVSV- and DNA-based vaccine platforms . The mRNA EBOV-GP vaccine , formulated in lipid nanoparticles , elicited significantly higher levels of total IgG and neutralizing antibody titers compared to the rVSV-EBOV-GP vaccine. Linear antibody epitope analysis indicated a preference for targeting the mucin-like domain in EBOV-GP1 following rVSV-based vaccination, while the mRNA platform distinc...

The #receptor #binding properties of #H5Ny #influenza A viruses have evolved to bind to avian-type mucin-like O-glycans

  Abstract Highly pathogenic H5Ny 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 H5Ny 2.3.4.4b viruses bind core 3 sialyl-Lewisx and Sia-Gal-β3GalNAc, O-linked glycans not recognized by classical H5 or other avian viruses . By determining crystal structures, we resolved the structural features of four glycans in an H5 hemagglutinin (HA) from a 2016 2.3.4.4b virus . While these viruses do not bind human-type receptors , their broad receptor specificity enhances...

#Infection and #transmission dynamics of #bovine and #human #influenza A #H5N1 viruses in mouse and hamster #models

  Abstract Here we investigated the pathogenesis and contact transmission of bovine- and human-derived highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b genotype B3.13 viruses in mammalian models . Using reverse genetics , we rescued three naturally occurring viruses : rTX2/24 (bovine-derived), rTexas/37 and rMichigan/90 (both human-derived), and compared their infection dynamics , replication and pathogenicity with the wild-type bovine TX2/24 strain in vitro and in vivo . All four viruses demonstrated comparable replication kinetics in four mammalian cell lines. However, the rMichigan/90 strain exhibited significantly smaller plaques in bovine and human cells . In vivo studies showed that mice infected with any of the viruses succumbed to infection within 4-5 days ; however, mice infected with the rMichigan/90 virus exhibited slightly lower viral replication and shedding compared to the other strains. Similarly, as in the mouse experiments, in hamsters, all viruses indu...

Association between #COVID19 #vaccine efficacy and #epidemic force of #infection

  Abstract The association between vaccine efficacy (VE) and force of infection (FoI) remains incompletely understood . Previous analyses have been primarily based on trial-level summary data—not accounting for the effect of time and constrained by the number of trials. Here, we leverage individual-level data from three phase 3 randomized, placebo-controlled COVID-19 vaccine trials —the COVE trial (Moderna, CoVPN3001), the AZD1222 trial (AstraZeneca, CoVPN3002), and the ENSEMBLE trial (Janssen/Johnson & Johnson, CoVPN3003)—and contemporaneous geographic-location-specific SARS-CoV-2 surveillance data from the start of the pandemic through November 14, 2021 (including the blinded follow-up periods of the trials) to conduct five cohort- and vaccine-specific analyses: COVE (U.S.), AZD1222 overall (U.S. + non-U.S.), AZD1222 U.S., ENSEMBLE overall (U.S. + non-U.S.), and ENSEMBLE U.S. In AZD1222 U.S., higher VE was associated with higher FoI (p = 0.01). In ENSEMBLE overall, lower VE w...

Iustitia, Maerten van Heemskerck (1556)

  Public Domain. Source:  Link:  https://www.wikiart.org/en/maerten-van-heemskerck/iustitia ____

Modeling of #H5N1 #influenza virus #kinetics during dairy #cattle #infection suggests the timing of infectiousness

  Abstract Since early-2024 unprecedented outbreaks of highly pathogenic avian influenza H5N1 clade 2.3.4.4b have been ongoing in dairy cattle in the United States with significant consequences for the dairy industry and public health . Estimation of key epidemiological parameters is required to support outbreak response , including predicting the likely effectiveness of interventions and testing strategies . Here, we pool limited publicly available data from four studies of naturally and experimentally infected dairy cattle. We quantify Ct value trajectories of infected dairy cattle and the relationship between Ct value and the log-titer of infectious virus , a proxy for infectiousness . We estimate that following infection minimum Ct values are rapidly reached within 1–2 days with a population mean Ct value of 15.7 (12.9, 18.4). We identify a threshold Ct value of 21.8 (19.9, 24.6), with values of Ct value above this threshold representing little-to-no infectious viral load . Fin...

#Bovine-derived #influenza A virus #H5N1 shows efficient #replication in well-differentiated #human #nasal epithelial cells without requiring genetic #adaptation

  Abstract Highly pathogenic avian influenza H5N1 viruses of clade 2.3.4.4b have caused widespread avian mortality and sporadic mammalian infections , raising concerns about their potential for efficient replication in the human population . Efficient replication in the human upper respiratory tract is considered a key barrier to transmission . Here, we demonstrate that an H5N1 virus isolated from bovine milk in Texas in 2024 (H5N1Tex/24) replicates as efficiently as the 2009 pandemic H1N1 virus (H1N1HH4/09) in well-differentiated human nasal epithelial cells . These cells express both avian- and human-type influenza receptors , indicating receptor adaptation is unnecessary for entry . H5N1Tex/24 replicates effectively at 33 degrees Celsius , reflecting nasal cavity temperature , whereas earlier avian H5N1 strains require 37 degrees Celsius, suggesting that H5N1Tex/24 has acquired another key adaptive feature to the human upper respiratory tract. H5N1Tex/24 remains sensitive to int...