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Alarmin S100A9 restricts retroviral infection by limiting reverse transcription in human dendritic cells
Author(s) -
Maarifi Ghizlane,
Lagisquet Justine,
Hertel Quentin,
Bonaventure Boris,
Chamontin Célia,
Fuchs Kyra,
Moncorgé Olivier,
Tauziet Marine,
Mombled Margaux,
Papin Laure,
Molès JeanPierre,
Bodet Charles,
Lévèque Nicolas,
Gross Antoine,
Arhel Nathalie,
Nisole Sébastien,
Van de Perre Philippe,
Goujon Caroline,
Blanchet Fabien P
Publication year - 2021
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2020106540
Subject(s) - biology , reverse transcriptase , intracellular , microbiology and biotechnology , transcription factor , immune system , dendritic cell , gene silencing , virology , immunology , genetics , rna , gene
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.