Alarmin S100A9 restricts retroviral infection by limiting reverse transcription in human dendritic cells.
Ghizlane MaarifiJustine LagisquetQuentin HertelBoris BonaventureCélia ChamontinKyra FuchsOlivier MoncorgéMarine TauzietMargaux MombledLaure PapinJean-Pierre MolèsCharles BodetNicolas LévèqueAntoine GrossNathalie ArhelSébastien NisolePhilippe Van de PerreCaroline GoujonFabien P BlanchetPublished in: The EMBO journal (2021)
Dendritic cells (DC) subsets, like Langerhans cells (LC), are immune cells involved in pathogen sensing. They express specific antimicrobial cellular factors that are able to restrict infection and limit further pathogen transmission. Here, we identify the alarmin S100A9 as a novel intracellular antiretroviral factor expressed in human monocyte-derived and skin-derived LC. The intracellular expression of S100A9 is decreased upon LC maturation and inversely correlates with enhanced susceptibility to HIV-1 infection of LC. Furthermore, silencing of S100A9 in primary human LC relieves HIV-1 restriction while ectopic expression of S100A9 in various cell lines promotes intrinsic resistance to both HIV-1 and MLV infection by acting on reverse transcription. Mechanistically, the intracellular expression of S100A9 alters viral capsid uncoating and reverse transcription. S100A9 also shows potent inhibitory effect against HIV-1 and MMLV reverse transcriptase (RTase) activity in vitro in a divalent cation-dependent manner. Our findings uncover an unexpected intracellular function of the human alarmin S100A9 in regulating antiretroviral immunity in Langerhans cells.
Keyphrases
- dendritic cells
- endothelial cells
- hiv infected
- hiv positive
- antiretroviral therapy
- human immunodeficiency virus
- hiv aids
- poor prognosis
- induced pluripotent stem cells
- hepatitis c virus
- immune response
- mass spectrometry
- pluripotent stem cells
- simultaneous determination
- hiv testing
- men who have sex with men
- hiv infected patients
- staphylococcus aureus
- reactive oxygen species
- transcription factor
- regulatory t cells
- sars cov
- liquid chromatography
- candida albicans
- peripheral blood
- cell death
- long non coding rna
- high resolution
- soft tissue