ETIDIOH - NEW

  Abstract In recent years, the four main swine influenza A virus (IAV-S) subtypes circulating in swine in the EU have been H1avN1, H1huN2, H1N1pdm09, and H3N2 . The latter emerged in 1984 from a reassortment event between a human seasonal H3N2 and H1avN1, and is currently detected at low prevalence in swine in Italy . Here, we describe nine H3N2 IAV-S isolates belonging to three novel genotypes , first detected in Italy in 2021 , likely resulting from reassortment events between swine and human IAVs. The first genotype was characterized by a hemagglutinin (H3 HA) of human seasonal origin , a neuraminidase (N2 NA) derived from H1huN2 strains circulating in Italian swine, and an avian-like internal gene cassette (IGC). The second genotype differed in its IGC constellation: PB2, PB1, PA and NP segments were of pandemic origin ( pdm09 ), while NS and M segments derived from the Eurasian avian-like lineage . The third genotype combined a human-derived H3, a Gent/84-derived N2, and a pd...

  Abstract Influenza A virus (IAV) infection is associated with a wide variety of neurological complications , of which mild complications like impaired cognitive functioning are most prominent . Even though several studies have shown that many influenza viruses can enter the CNS, the neuropathogenesis of seasonal ( H3N2 and H1N1 ) and pandemic (pH1N1 2009) IAV infections is poorly understood. Therefore, we aimed to investigate the cellular tropism, replication efficiency and associated functional consequences using a human stem cell-derived neural co-culture model of neurons and astrocytes . All viruses were able to infect neurons in the co-culture model, although this infection did not result in efficient replication and release of progeny virus. In addition, infection did not result in visible cell death or apoptosis. However, functional analyses revealed that IAV inoculation resulted in a reduction of spontaneous neural activity and a partial reduction of neural excitability. T...

  ABSTRACT Influenza A virus (IAV) in swine in the U.S. is surveilled to monitor genetic evolution to inform intervention efforts and aid pandemic preparedness . We describe data from the U.S. Department of Agriculture National Surveillance Plan for Influenza A Virus in Pigs from 2009 to 2022. Clinical respiratory cases were subtyped, followed by sequencing of hemagglutinin (HA) and neuraminidase (NA), and a subset of viruses was whole genome sequenced . Phylogenetic analysis identified geographic and temporal IAV reassortment hotspots . Regions acting as IAV genomic diversity sources or sinks were quantified, and dissemination was qualified and modeled. The dominant IAV clades were H1N2 (1B.2.1), H3N2 (1990.4.a), and H1N1 (H1-1A.3.3.3-c3). Internal genes were classified as triple-reassortant (T) or pandemic 2009 (P), and three genome constellations represented 73.5% of detections across the last 2 years. In some years, the distribution of IAV diversity was so narrow that it presen...

Abstract Background .  Highly pathogenic avian influenza A(H5) viruses pose a pandemic threat , with a history of zoonotic spillovers into humans that are presumed immunologically naive. Whether the general population is currently immunologically naive to circulating A(H5) influenza viruses is unknown.  Methods .  To evaluate the presence of cross-reactive immune responses to emerging A(H5) clade 2.3.4.4b influenza viruses in the general population, we conducted comprehensive immune profiling on cross-sectional samples from healthcare workers (n=107). Samples were collected in August and September 2024 in the scope of an ongoing prospective follow-up study: Surveillance of rEspiratory viruses iN healThcare and anImal workers in the NethErLands (SENTINEL).  Findings .  Low-level antibody responses directed against the A(H5) hemagglutinin (HA) head were detected in a limited number of individuals , but without hemagglutination inhibition activity. Nevertheless, we...

Abstract Influenza A virus (IAV) poses a significant global health risk, with highly pathogenic strains like H5N1 (CFR ~52%) causing severe disease compared to less lethal but more transmissible strains like H1N1 (CFR 0.01-0.03%). Although IAV primarily infects lung epithelial cells , causing cell death and tissue damage , the molecular basis of strain-specific pathogenesis remains poorly understood. Here we show that in cell culture , H5N1 induced more rapid and extensive cell death than H1N1. Since Interferon (IFN) signaling is key to innate immunity, we examined its role in virus-induced cell death using STAT1-knockout A549 cells and JAK/STAT pathway inhibitors like Baricitinib . Both approaches reduced cell death across various IAV strains, including H1N1, H5N1, H7N9 , and H3N2 . However, inhibition increased viral titers , raising concerns about its clinical use in isolation. To overcome this, we tested a combination of Oseltamivir (antiviral) and Baricitinib (anti-inflammatory). ...

Abstract The H1N1 swine influenza viruses CQ91 and CQ445, isolated from pigs in China, exhibited distinct virulence in mice despite sharing similar genomic constellations. CQ91 demonstrated higher pathogenicity (MLD50: 5.4 log10 EID50) and replication efficiency in mice compared to CQ445 (MLD50: 6.6 log10 EID50). Through reverse genetics, we found that the attenuation of CQ445 was due to a single substitution of glutamic acid (E) with lysine (K) at position 343 in the PB2 protein . Introducing the CQ445-PB2 (343K) into CQ91 significantly reduced viral replication and pathogenicity in mice, while replacing CQ445-PB2 with CQ91-PB2 (343E) restored virulence. In vitro studies showed that the K343E mutation impaired viral replication in MDCK and A549 cells and reduced polymerase activity in minigenome assays. Mechanistically, the amino acid at position 343 in the PB2 affects the transcription stage of the viral replication process . Structural modeling indicated that the charge reversal cau...

Abstract Highly pathogenic avian influenza of the H5N1 subtype has shown recent unprecedented expansion in its geographic and host range , increasing the pandemic threat . The younger age of H5N1 versus H7N9 avian influenza in humans has previously been attributed to imprinted pre-immunity to hemagglutinin stalk (HA2) epitopes shared with group 1 ( H1N1, H2N2 ) versus group 2 ( H3N2 ) influenza A subtypes predominating in the human population before versus after 1968, respectively. Here we review the complex immuno-epidemiological interactions underpinning influenza risk assessment and extend the imprinting hypothesis to include a potential role for cross-protective neuraminidase (NA) imprinting . We compare H5N1 distributions and case fatality ratios by age and birth cohort (as proxy for HA2 and/or NA imprinting epoch) not only to H7N9 but also H5N6 and H9N2 avian influenza, representing more varied conditions of zoonotic influenza relatedness to human subtypes of the past century. We...

Abstract Background From 1918 to 1920, the largest influenza A virus (IAV) pandemic known to date spread globally causing between 20 to 100 million deaths . Historical records have captured critical aspects of the disease dynamics , such as the occurrence and severity of the pandemic waves . Yet, other important pieces of information such as the mutations that allowed the virus to adapt to its new host can only be obtained from IAV genomes. The analysis of specimens collected during the pandemic and still preserved in historical pathology collections can significantly contribute to a better understanding of its course. However, efficient RNA processing protocols are required to work with such specimens. Results Here, we describe an alternative protocol for efficient ancient RNA sequencing and evaluate its performance on historical samples, including a published positive control. The phenol/chloroform-free protocol efficiently recovers ancient viral RNA , especially small fragments , an...

Abstract The Eurasian avian-like swine (EA) H1N1 virus has been widely prevalent in the Chinese swine population and has caused infections in human . However, knowledge regarding its pathogenic mechanisms remains limited. In this study, we analyzed the pathogenic determinants of two G4 genotype EA H1N1 viruses (A/Swine/Guangdong/SS12/2017 and A/Swine/Jiangxi/1110/2017) with differing pathogenicity by constructing a series of reassortant and mutant viruses . The HA-G219A mutation was found to be determinant of pathogenicity in mice. Subsequent analyses revealed that this mutation enhances viral replication in human cells , improves thermal stability , reduces HA activation pH, and alters receptor-binding properties . Furthermore, HA-G219A mutation may be an adaptive mutation that facilitates influenza virus adaptation to swine , with its prevalence increasing in the swine population. This mutation may support cross-species transmission of EA H1N1 swine influenza viruses or genetic excha...

Abstract The ecological factors that led to the 1918 influenza pandemic remain unknown. We hypothesise that horses acted as intermediate hosts spreading a pre-pandemic avian-origin virus before 1918. This is supported by reports describing a large epizootic of unusually severe equine influenza beginning in 1915. Furthermore, the high horse demand during WWI resulted in one of the biggest equine mobilisations in North America between 1914 and 1918. This extensive movement of horses provided abundant opportunities for virus reassortment between pre-pandemic avian and human influenza viruses. Archived equine tissues or serum samples will be needed to test this hypothesis. Source: Journal of Infectious Diseases,  https://academic.oup.com/jid/advance-article-abstract/doi/10.1093/infdis/jiaf197/8115353?redirectedFrom=fulltext&login=false ____

Influenza at the human-animal interface Summary and risk assessment, from 21 January to 19 March 2025 {1}  New human cases {2}:  From 21 January to 19 March 2025, based on reporting date , the detection of influenza A( H5N1 ) in five humans, influenza A( H9N2 ) virus in four humans, influenza A( H1N1 ) variant ((H1N1)v) virus in one human, and influenza A( H1N2 )v virus in one human were reported officially.  • Circulation of influenza viruses with zoonotic potential in animals:  -- High pathogenicity avian influenza (HPAI) events in poultry and non-poultry continue to be reported to the World Organisation for Animal Health (WOAH).{3}  The Food and Agriculture Organization of the United Nations (FAO) also provides a global update on avian influenza viruses with pandemic potential.{4}  • Risk assessment {5}:  -- Sustained human to human transmission has not been reported from these events. Based on information available at the time of the risk assessmen...

Abstract Influenza A viruses (IAV) are primarily transmitted between mammals by the respiratory route , and encounter bacteria in the respiratory tract before infecting susceptible epithelial cells. Previous studies have shown that mammalian-origin IAV can bind to the surface of different bacterial species and purified bacterial lipopolysaccharides (LPS), but despite the broad host range of IAV, few studies have included avian-origin IAV in these assessments. Since IAV that circulate in humans and birds are well-adapted to replication in the human respiratory and avian gastrointestinal tracts , respectively, we investigated the ability of multiple human and avian A(H1N1) IAV to associate with bacteria and their surface components isolated from both host niches. Binding interactions were assessed with microbial glycan microarrays, revealing that seasonal and avian IAV strains exhibited binding diversity to multiple bacterial glycans at the level of the virus and the bacterium, independe...

February 2025  The development of influenza candidate vaccine viruses (CVVs),  coordinated by WHO, remains an essential component of the overall global  strategy for influenza pandemic preparedness . Selection and development of  CVVs are the first steps towards timely vaccine production and do not imply a  recommendation for initiating manufacture. National authorities may consider the  use of 1 or more of these CVVs for pilot lot vaccine production, clinical trials and  other pandemic preparedness purposes based on their assessment of public health  risk and need. Zoonotic influenza viruses continue to be identified  and evolve both antigenically and genetically, leading to the need for additional  CVVs for pandemic preparedness purposes. Changes in the antigenic and genetic  characteristics of these viruses relative to existing CVVs and their potential risks  to public health justify the need to develop new CVVs. This docume...

Highlights •  Scientific question :  Cross-species transmission of influenza A viruses from swine to humans occurs occasionally because their tracheal epitheliums possess both sialic acid α-2,6-Gal and α-2,3-Gal receptors . In 2011, the first human case of swine influenza virus infection in the mainland of China was detected in Jiangsu Province . Subsequently, the Eurasian avian-like H1N1 swine influenza virus (EAH1N1 SIV) had sporadically crossed the host barrier and infected humans, raising public concern for its pandemic potential. •  Evidence before this study :  A/Jiangsu/1/2011 (H1N1v) was first discovered in 2011 and belongs to the G1 genotype. The G4 and G5 genotypes that appeared successively in 2013 are recombinant H1N1 swine influenza viruses. The EAH1N1 SIVs from 2016 to the present are dominated by the G4 genotype, with hemagglutination (HA) and neuraminidase (NA) genes derived from the EAH1N1 SIVs, non-structural protein (NS) genes derived from the trip...

The World Health Organization (WHO) today announced the recommendations for the viral composition of influenza vaccines for the 2025-2026 influenza season in the northern hemisphere.  The announcement was made at an information session at the end of a 4-day meeting on the Composition of Influenza Virus Vaccines, a meeting that is held twice annually.  WHO organizes these consultations with an advisory group of experts gathered from WHO Collaborating Centres and WHO Essential Regulatory Laboratories to analyse influenza virus surveillance data generated by the WHO Global Influenza Surveillance and Response System (GISRS).  The recommendations issued are used by the national vaccine regulatory agencies and pharmaceutical companies to develop, produce, and license influenza vaccines for the following influenza season.  The periodic update of viruses contained in influenza vaccines is necessary for the vaccines to be effective due to the constant evolving nature of influ...