ArticlePLoS pathogens2018
Internal genes of a highly pathogenic H5N1 influenza virus determine high viral replication in myeloid cells and severe outcome of infection in mice.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- Pathogenesis and Transmission of a Reassorted H1 Influenza A Virus Detected in North American Swine.Influenza and other respiratory viruses · 2026Article
- Internal gene segments from a mouse-adapted influenza B virus confer increased pathogenicity to mice.PloS one · 2026Article
- Innate immune role of IL-6 in influenza a virus pathogenesis.Frontiers in cellular and infection microbiology · 2025Review
- STING regulates NETs formation by activating GSDMD in influenza viral pneumonia.Frontiers in immunology · 2025Article
- Amino acids in the polymerase complex of shorebird-isolated H1N1 influenza virus impact replication and host-virus interactions in mammalian models.Emerging microbes & infections · 2024Article
- Defining the balance between optimal immunity and immunopathology in influenza virus infection.Nature reviews. Immunology · 2024Review
- Generation of a Porcine Cell Line Stably Expressing Pig TMPRSS2 for Efficient Isolation of Swine Influenza Virus.Pathogens (Basel, Switzerland) · 2023Article
- An Influenza A virus can evolve to use human ANP32E through altering polymerase dimerization.Nature communications · 2023Article
- A Novel Triple Reassortment H3N8 Avian Influenza Virus: Characteristics, Pathogenicity, and Transmissibility.Transboundary and emerging diseases · 2023Article
- Generation of porcine PK-15 cells lacking the Ifnar1 or Stat2 gene to optimize the efficiency of viral isolation.PloS one · 2023Article
- Levels of Influenza A Virus Defective Viral Genomes Determine Pathogenesis in the BALB/c Mouse Model.Journal of virology · 2022Article
- Naïve Human Macrophages Are Refractory to SARS-CoV-2 Infection and Exhibit a Modest Inflammatory Response Early in Infection.Viruses · 2022Article
- A Review and Meta-Analysis of Influenza Interactome Studies.Frontiers in microbiology · 2022Review
- Effects of Receptor Specificity and Conformational Stability of Influenza A Virus Hemagglutinin on Infection and Activation of Different Cell Types in Human PBMCs.Frontiers in immunology · 2022Article
- Hallmarks of Severe COVID-19 Pathogenesis:Frontiers in immunology · 2022Review
- Neutrophils in respiratory viral infections.Mucosal immunology · 2021Review
- The furin cleavage site in the SARS-CoV-2 spike protein is required for transmission in ferrets.Nature microbiology · 2021Article
- Article
- R848 or influenza virus can induce potent innate immune responses in the lungs of neonatal mice.Mucosal immunology · 2021Article
- Structure and Function of the Influenza Virus Transcription and Replication Machinery.Cold Spring Harbor perspectives in medicine · 2020Review
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
The highly pathogenic avian influenza (HPAI) H5N1 influenza virus has been a public health concern for more than a decade because of its frequent zoonoses and the high case fatality rate associated with human infections. Severe disease following H5N1 influenza infection is often associated with dysregulated host innate immune response also known as cytokine storm but the virological and cellular basis of these responses has not been clearly described. We rescued a series of 6:2 reassortant viruses that combined a PR8 HA/NA pairing with the internal gene segments from human adapted H1N1, H3N2, or avian H5N1 viruses and found that mice infected with the virus with H5N1 internal genes suffered severe weight loss associated with increased lung cytokines but not high viral load. This phenotype did not map to the NS gene segment, and NS1 protein of H5N1 virus functioned as a type I IFN antagonist as efficient as NS1 of H1N1 or H3N2 viruses. Instead we discovered that the internal genes of H5N1 virus supported a much higher level of replication of viral RNAs in myeloid cells in vitro, but not in epithelial cells and that this was associated with high induction of type I IFN in myeloid cells. We also found that in vivo during H5N1 recombinant virus infection cells of haematopoetic origin were infected and produced type I IFN and proinflammatory cytokines. Taken together our data infer that human and avian influenza viruses are differently controlled by host factors in alternative cell types; internal gene segments of avian H5N1 virus uniquely drove high viral replication in myeloid cells, which triggered an excessive cytokine production, resulting in severe immunopathology.
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