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#Haemagglutinin 162-164 #deletions enhance #influenza B/Victoria virus #fitness and #virulence in vivo

  Abstract Influenza B viruses cause substantial respiratory disease and seasonal outbreaks. Despite decades of circulation in humans , only the B/Victoria lineage persisted after the COVID-19 pandemic. Continual evolution has generated hemagglutinin deletion variants at residues 162-164 that drive successive epidemics , yet their functional consequences remain poorly understood. Using integrated phylodynamics and reverse genetics , we show that Clade V1A.1 viruses carrying a two-amino acid deletion exhibit enhanced replication and increased virulence compared with ancestral viruses lacking deletions. The recently prevailing Clade V1A.3 , which harbors a three-amino acid deletion together with the K136E substitution, has completely displaced V1A.1 and causes more severe disease in mice . Both clades bound efficiently to alpha 2-3 and 2-6 sialylated glycans and exhibited broad tolerance to acidic pH and elevated temperatures . These findings reveal that specific combinations of HA d...

History of Mass Transportation: The Fiat FS ETR.401 Electric Multiple Unit

  Di maurizio messa - Flickr: FS ETR401, CC BY-SA 2.0,  https://commons.wikimedia.org/w/index.php?curid=20276434 Source:  Link:  https://it.wikipedia.org/wiki/Fiat_Ferroviaria ____

#Pathogenesis and #Research #Models of Acute #Influenza-Associated #Encephalitis / #Encephalopathy: An Update

  Abstract Influenza-associated encephalitis/encephalopathy (IAE) is a severe neurological complication characterized by central nervous system dysfunction and structural damage following influenza virus infection . Predominantly affecting infants and young children , IAE exhibits its highest incidence in those under five years of age . Key clinical manifestations of IAE include acute seizures, sudden high fever, and impaired consciousness , frequently progressing to coma . Neuroimaging , particularly magnetic resonance imaging (MRI), often reveals multifocal brain lesions involving multiple brain regions, including the cerebellum, brainstem, and corpus callosum . The prognosis of IAE is poor , with a mortality rate reaching 30%. Current diagnosis relies heavily on clinical presentation and characteristic neuroimaging findings, as the precise pathogenesis of IAE remains elusive . While various research models, including cell lines, brain organoids, and animal models , have been dev...

#USA, #Wastewater Data for Avian #Influenza #H5 (#CDC, Jan. 8 '26)

  {Excerpt} Time Period: December 28, 2025 - January 03, 2026 -- H5 Detection :  3 site(s) ( 0.7% ) -- No Detection :  428 site(s) ( 99.3% ) -- No samples in last week :  111 site(s) (...) Source:  Link:  https://www.cdc.gov/nwss/rv/wwd-h5.html ____

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

  {A barnacle goose} By Andreas Trepte - Own work, CC BY-SA 2.5,  https://commons.wikimedia.org/w/index.php?curid=32487518 ___ In accordance with the WOAH Terrestrial Animal Health Code, Article 10.4.1, point 4, this outbreak does not change the disease-free status of Sweden as these are wild birds or birds kept in a single household, and therefore do not fall within the WOAH definition of poultry. {Sjöbo Region} A barnacle goose was killed. It was sent to the Swedish Veterinary Agency for laboratory analysis as part of the national surveillance program for avian influenza. Source:  Link:  https://wahis.woah.org/#/in-review/7180 ____

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

  Affected avian species were grazing ducks in Davao del Sur Region. Source:  Link:  https://wahis.woah.org/#/in-review/7105 ____

One confirmed and one potential #human case of #influenza #H5N1 detected through an expanded subtyping protocol

  ABSTRACT Current U.S. surveillance for highly pathogenic avian influenza A(H5N1) in humans prioritizes individuals with known animal exposures , potentially missing community-acquired infections . To address this gap, we implemented universal H5 subtyping of all influenza A-positive respiratory samples collected within our hospital system , regardless of patient exposure history. Between August 2024 and April 2025, we subtyped 4,488 influenza A-positive samples and identified two cases positive for H5 RNA in Alameda County, California, USA . The first case was a 14-month-old girl with mild respiratory symptoms and no H5N1 exposure risks ; sequencing of the sample revealed an H5 gene closely related to clade 2.3.4.4b, genotype B3.13 viruses circulating in U.S. dairies . The second case was a 79-year-old male, also with no known exposures , whose sample reproducibly tested positive with a high cycle threshold value but could not be confirmed by public health laboratories. Both pati...

Within-host adaptive #evolution is limited by genetic #drift in experimental #human #influenza A virus #infections

  Abstract Selection of advantageous mutations drives the emergence of dominant variants during seasonal influenza epidemics . However, within-host detection of such variants remains rare , limiting our understanding of how selection operates at the scale of individual hosts. In this study, we used a controlled human infection model to examine the within-host evolutionary dynamics in thirteen participants intranasally infected with a seasonal H3N2 influenza A virus . Although this clinical trial is ongoing , our work represents a pre-planned, interim, exploratory analysis. Results in this system were contrasted with those observed in a ferret model of infection. The inoculum, used in both humans and ferrets, carried standing diversity that enabled evaluation of variant trajectories during infection. Although the dynamics were variable among participants, in humans , the minor variants in the PA and NP gene segments tended to increase in frequency as infection progressed. Variant dy...

#Poland - High pathogenicity avian #influenza #H5N1 viruses (Inf. with) (#poultry) - Follow up report 2

  Poultry farms in Podlaskie Region. Source:  Link:  https://wahis.woah.org/#/in-review/7177 ____

#Lassa fever #symptomatology, viral dynamics, and host immune response (PREPARE): a prospective, observational cohort study in #Liberia

  Summary Background Lassa virus (LASV) is a persistent threat to public health in west Africa and beyond . LASV is endemic in west Africa and each year it is responsible for an estimated 2·7 million infections, 23 700 hospitalisations, and 5000 deaths . With over 32 reported cases of Lassa fever imported into non-endemic countries—one-third of which were fatal—the importance of enhanced detection and management of Lassa fever extends beyond west Africa. Methods The prevalence, pathogenesis, and persistence (PREPARE) study was a prospective cohort study among patients admitted to two hospitals in a hyperendemic area of Liberia . Any patients aged 5 years or older with a febrile illness were eligible to enrol and be tested for Lassa fever. The study aimed to measure the prevalence of LASV infection and assess the signs and symptoms, LASV viral replication kinetics, and LASV-specific IgM and IgG responses longitudinally among adults and children with laboratory-confirmed Lassa fever....

Adjuvanted #influenza #vaccination increases pre-existing #H5N1 cross-reactive #antibodies

  Abstract Highly pathogenic H5N1 avian influenza viruses of clade 2.3.4.4b cause sporadic human infections and currently raise concerns about a new influenza pandemic . Heterogeneities in disease severity have been observed in the past and are reported among infected farm workers in the United States . These may be attributed to differences in pre-existing H5N1 cross-reactive antibodies . In this study, we characterize H5N1 cross-reactive antibody landscapes in the current population (#NCT05794412 and #NCT01022905) and assess the effect of AS03-adjuvanted pandemic H1N1 and non-adjuvanted seasonal influenza vaccination on H5N1 cross-neutralizing and IgG antibody titers targeting a range of influenza virus-derived antigens. We detect H5N1 cross-neutralizing antibodies using a vesicular stomatitis virus-based pseudovirus system that correlate well with antibodies inhibiting the spread of authentic H5N1 viruses, anti-group 1 hemagglutinin stalk and anti-trimeric hemagglutinin antibodi...

Structural basis for #human #DPP4 #receptor recognition by #MERS-like #coronaviruses 2014-422 and GX2012

  Abstract Since its emergence in 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has posed a significant threat to human health . Recently, novel MERS-like coronaviruses with the potential for cross-species transmission have been identified. In this study, we focused on two newly isolated bat strains with putative health concern: BatCoV/Ii/GD/2014-422 (2014-422) and BtTp-BetaCoV/GX2012 (GX2012). We determined the cryo-EM structures of the spike glycoprotein trimer in the closed state for these two viruses. These structures display a more compact conformation compared to MERS-CoV spike . Biochemical characterization demonstrates that the spike receptor-binding domains (RBDs) of 2014-422 and GX2012 can bind to human dipeptidyl peptidase 4 (hDPP4). To investigate the structural determinants of pseudovirus infection, we solved the cryo-EM structures of 2014-422 RBD-hDPP4 and GX2012 RBD-hDPP4 complexes. The binding mode of the complex is conserved, but the angle of the RB...

#USA, #Massachusetts reports three #pediatric #deaths due to seasonal #influenza so far (DoH, Jan. 8 '26)

  Boston — The Massachusetts Department of Public Health (DPH) is reporting very high and rising levels of influenza activity statewide as the Commonwealth moves through peak flu season .  Thousands of residents have become ill , forcing them to miss work, school, and other activities.  Many are experiencing serious complications , leading to increased visits to urgent care centers and emergency departments, and high levels of hospitalization .  The current widespread burden of illness underscores the importance of taking preventive measures , especially vaccination , to reduce severe disease and protect individuals, families, and communities. Tragically, influenza has already been reported to be associated with the deaths of three pediatric patients in Massachusetts during recent weeks.  In addition, there have been 29 adult influenza deaths reported so far this season.  While COVID-19 and respiratory syncytial virus (RSV) rates currently remain low, cases...

Natural #H5N1 #immunity in dairy #cows is durable and cross-protective but non-sterilizing

  Abstract Ongoing transmission of influenza A virus (H5N1) in U.S. dairy cattle threatens both animal and human health , underscoring the need to understand the durability of host immunity against reinfection with evolving genotypes . We challenged naive and convalescent cows , infected one year prior with H5N1 genotype B3.13, with either homologous B3.13 or heterologous D1.1 genotype virus . Homologous rechallenge resulted in complete clinical protection with no infectious viral shedding . Conversely, heterologous rechallenge led to transient clinical disease and limited infectious viral shedding . Convalescent cows experienced significantly milder disease than naive cows, which developed severe illness with high viral shedding and required early euthanasia , regardless of the strain. These findings indicate that naturally acquired immunity offers strong protection against severe illness but may allow silent transmission of divergent strains . Therefore, natural herd immunity alo...

#mRNA-delivered neutralizing #antibodies confer protection against #SARS-CoV-2 in animal #models

  ABSTRACT Monoclonal antibodies represent potent biological countermeasures against a wide range of human diseases ; however, their clinical application and widespread use are limited by the high cost and complexity of antibody production and manufacturing. The mRNA-lipid nanoparticle (mRNA-LNP) platform offers a versatile strategy for vaccine development and protein-replacement therapies. Since the COVID-19 pandemic, a number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)- neutralizing antibodies have been identified, with several granted emergency use authorization for patients. Here, we report the design and generation of mRNA-LNPs encoding two SARS-CoV-2-neutralizing antibodies , 76E1 and LY1404, which, respectively, target the spike protein’s fusion peptide (FP) and receptor-binding domain (RBD). We demonstrated that a single intramuscular administration of these mRNA-LNPs in mice resulted in robust antibody production that sustained in circulation for 7–14 d...

Intrahost HA #polymorphisms and culture #adaptation shape antigenic profiles of #H3N2 #influenza viruses

  ABSTRACT Accurate antigenic characterization of influenza viruses is critical for vaccine strain selection but is often confounded by intrahost genetic diversity and culture-induced adaptations . We analyzed 60 A(H3N2)-positive nasopharyngeal specimens collected during the 2017–2018 influenza season to determine how virus propagation in MDCK cells affects viral genetic and antigenic properties . Deep sequencing revealed frequent genome-wide intrahost polymorphisms , including amino acid variants within major hemagglutinin (HA) antibody-binding sites . Virus propagation imposed rapid purifying selection, markedly reducing intrahost genetic diversity . Serological analyses demonstrated that these selective events altered antigenic properties, indicating that culture adaptation can alter antigenic profiles . To assess the functional impact of HA polymorphisms, we generated mixed viral populations containing defined ratios of HA-160K, HA-160T, and HA-160I variants identified in clini...

#UK [#Scotland] - High pathogenicity avian #influenza #H5N1 viruses (Inf. with) (#poultry) - Immediate notification

  {Scotland} A small commercial poultry premise. Samples taken were positive for HPAI H5N1. Birds presented clinical signs prior to testing. Source:  Link:  https://wahis.woah.org/#/in-review/7173 ____

#Influenza hemagglutinin subtypes have different #sequence constraints despite sharing extremely similar #structures

  Abstract Hemagglutinins (HA) from different influenza A virus subtypes share as little as ~40% amino acid identity , yet their protein structure and cell entry function are highly conserved . Here we examine the extent that sequence constraints on HA differ across three subtypes . To do this, we first use pseudovirus deep mutational scanning to measure how all amino-acid mutations to an H7 HA affect its cell entry function. We then compare these new measurements to previously described measurements of how all mutations to H3 and H5 HAs affect cell entry function . We find that ~50% of HA sites display substantially diverged preferences for different amino acids across the HA subtypes. The sites with the most divergent amino-acid preferences tend to be buried and have biochemically distinct wildtype amino acids in the different HA subtypes. We provide an example of how rewiring the interactions among contacting residues has dramatically shifted which amino acids are tolerated at s...

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

  A fattening turkey holding in Csongrád-Csanád Region. Source:  Link:  https://wahis.woah.org/#/in-review/7172 ____

#Adaptation differences and mechanisms of #influenza viruses to ANP32 #proteins across #species

  ABSTRACT Avian influenza virus cross-species infection in humans poses a major threat to global public health . Species-specific differences between avian ANP32A and mammalian ANP32 proteins create a natural barrier against viral cross-species infection by directly impairing the functional interaction between the avian-origin viral RNA polymerase and mammalian ANP32 proteins , thereby restricting viral genome replication . The key to overcoming this barrier lies in the adaptation of viral RNA polymerase to host ANP32 family proteins . This mini-review summarizes the mechanisms and variations in influenza virus adaptation to ANP32 proteins across different species. Influenza viruses adapt to species-specific ANP32 proteins through various mutations and display distinct preferences for specific ANP32 family members within the same host. Additionally, alternative splicing variants of ANP32A within a single species further modulate viral RNA polymerase adaptability. Despite this dive...