Wichit S. auteur aut IRD Hamel Rodolphe auteur aut IRD Zanzoni A. auteur aut IRD Diop F. auteur aut IRD Cribier A. auteur aut IRD Talignani L. auteur aut IRD Diack A. auteur aut IRD Ferraris Pauline auteur aut IRD Liégeois Florian auteur aut IRD Urbach S. auteur aut IRD Ekchariyawat P. auteur aut IRD Merits A. auteur aut IRD Yssel H. auteur aut IRD Benkirane M. auteur aut IRD Missé Dorothée auteur aut IRD text journalArticle eng text/pdf reformatted digital access Chikungunya virus (CHIKV) and Zika virus (ZIKV) are emerging arboviruses that pose a worldwide threat to human health. Currently, neither vaccine nor antiviral treatment to control their infections is available. As the skin is a major viral entry site for arboviruses in the human host, we determined the global proteomic profile of CHIKV and ZIKV infections in human skin fibroblasts using Stable Isotope Labelling by Amino acids in Cell culture (SILAC)-based mass-spectrometry analysis. We show that the expression of the interferon-stimulated proteins MX1, IFIT1, IFIT3 and ISG15, as well as expression of defense response proteins DDX58, STAT1, OAS3, EIF2AK2 and SAMHD1 was significantly up-regulated in these cells upon infection with either virus. Exogenous expression of IFITs proteins markedly inhibited CHIKV and ZIKV replication which, accordingly, was restored following the abrogation of IFIT1 or IFIT3. Overexpression of SAMHD1 in cutaneous cells, or pretreatment of cells with the virus-like particles containing SAMHD1 restriction factor Vpx, resulted in a strong increase or inhibition, respectively, of both CHIKV and ZIKV replication. Moreover, silencing of SAMHD1 by specific SAMHD1-siRNA resulted in a marked decrease of viral RNA levels. Together, these results suggest that IFITs are involved in the restriction of replication of CHIKV and ZIKV and provide, as yet unreported, evidence for a proviral role of SAMHD1 in arbovirus infection of human skin cells. specialized SAMHD1 arbovirus Chikungunya Zika IFIT SILAC 052 050 020 20 7 art. 1695 [18 ] 2019 1422-0067 https://www.documentation.ird.fr/hor/fdi:010075622 10.3390/ijms20071695 1422-0067 [F B010075622] https://www.documentation.ird.fr/hor/fdi:010075622 https://horizon.documentation.ird.fr/exl-doc/pleins_textes/divers19-05/010075622.pdf IRD - Base Horizon / Pleins textes 2019-06-04 2025-02-24 fdi:010075622 fre