Differential Modulation of Innate Immune Responses in Human Primary Cells by Influenza A Viruses Carrying Human or Avian Nonstructural Protein 1

Autor: Boris M. Hartmann, Stuart C. Sealfon, Miguel Fribourg, Ana Fernandez-Sesma, Irene Ramos, Nada Marjanovic, Uma Potla, Paula L. Monteagudo, Ignacio Mena, Raquel Muñoz-Moreno, Adolfo García-Sastre
Rok vydání: 2019
Předmět:
viruses
Cellular Response to Infection
Viral Nonstructural Proteins
Influenza A Virus
H7N9 Subtype
medicine.disease_cause
Madin Darby Canine Kidney Cells
Influenza A Virus
H1N1 Subtype
Influenza A virus
innate immunity
Phylogeny
Cellular localization
0303 health sciences
030302 biochemistry & molecular biology
Acquired immune system
Phenotype
3. Good health
interferons
Host-Pathogen Interactions
Tumor necrosis factor alpha
influenza
Reassortant Viruses
Primary Cell Culture
Immunology
Biology
Microbiology
Host Specificity
NS1 protein
Proinflammatory cytokine
Birds
Interferon-gamma
03 medical and health sciences
Dogs
Virology
medicine
Animals
Humans
dendritic cells
030304 developmental biology
Innate immune system
Influenza A Virus
H5N1 Subtype
Interleukin-6
Tumor Necrosis Factor-alpha
Influenza A Virus
H3N2 Subtype
Interferon-alpha
Epithelial Cells
Interferon-beta
Influenza A Virus
H7N2 Subtype
Immunity
Innate
Influenza A virus subtype H5N1
Gene Expression Regulation
Insect Science
Zdroj: Journal of Virology
ISSN: 1098-5514
0022-538X
DOI: 10.1128/jvi.00999-19
Popis: Influenza A viruses (IAVs) cause seasonal epidemics which result in an important health and economic burden. Wild aquatic birds are the natural host of IAV. However, IAV can infect diverse hosts, including humans, domestic poultry, pigs, and others. IAVs circulating in animals occasionally cross the species barrier, infecting humans, which results in mild to very severe disease. In some cases, these viruses can acquire the ability to be transmitted among humans and initiate a pandemic. The nonstructural 1 (NS1) protein of IAV is an important antagonist of the innate immune response. In this study, using recombinant viruses and primary human cells, we show that NS1 proteins from human and avian hosts show intrinsic differences in the modulation of the innate immunity in human dendritic cells and epithelial cells, as well as different cellular localization dynamics in infected cells.
The influenza A virus (IAV) nonstructural protein 1 (NS1) contributes to disease pathogenesis through the inhibition of host innate immune responses. Dendritic cells (DCs) release interferons (IFNs) and proinflammatory cytokines and promote adaptive immunity upon viral infection. In order to characterize the strain-specific effects of IAV NS1 on human DC activation, we infected human DCs with a panel of recombinant viruses with the same backbone (A/Puerto Rico/08/1934) expressing different NS1 proteins from human and avian origin. We found that these viruses induced a clearly distinct phenotype in DCs. Specifically, viruses expressing NS1 from human IAV (either H1N1 or H3N2) induced higher levels of expression of type I (IFN-α and IFN-β) and type III (IFN-λ1 to IFNλ3) IFNs than viruses expressing avian IAV NS1 proteins (H5N1, H7N9, and H7N2), but the differences observed in the expression levels of proinflammatory cytokines like tumor necrosis factor alpha (TNF-α) or interleukin-6 (IL-6) were not significant. In addition, using imaging flow cytometry, we found that human and avian NS1 proteins segregate based on their subcellular trafficking dynamics, which might be associated with the different innate immune profile induced in DCs by viruses expressing those NS1 proteins. Innate immune responses induced by our panel of IAV recombinant viruses were also characterized in normal human bronchial epithelial cells, and the results were consistent with those in DCs. Altogether, our results reveal an increased ability of NS1 from avian viruses to antagonize innate immune responses in human primary cells compared to the ability of NS1 from human viruses, which could contribute to the severe disease induced by avian IAV in humans. IMPORTANCE Influenza A viruses (IAVs) cause seasonal epidemics which result in an important health and economic burden. Wild aquatic birds are the natural host of IAV. However, IAV can infect diverse hosts, including humans, domestic poultry, pigs, and others. IAVs circulating in animals occasionally cross the species barrier, infecting humans, which results in mild to very severe disease. In some cases, these viruses can acquire the ability to be transmitted among humans and initiate a pandemic. The nonstructural 1 (NS1) protein of IAV is an important antagonist of the innate immune response. In this study, using recombinant viruses and primary human cells, we show that NS1 proteins from human and avian hosts show intrinsic differences in the modulation of the innate immunity in human dendritic cells and epithelial cells, as well as different cellular localization dynamics in infected cells.
Databáze: OpenAIRE
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