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SAMHD1 Enhances Chikungunya and Zika Virus Replication in Human Skin Fibroblasts

Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Nakhon Pathom 73170, Thailand
Laboratoire MIVEGEC, UMR 224 IRD/CNRS/UM1, 34394 Montpellier, France
Aix-Marseille Université, Inserm, TAGC UMR S1090, 13288 Marseille, France
Institut de Génétique Humaine, CNRS-Université de Montpellier, UMR 9002, 34090 Montpellier, France
Institut de Génétique Fonctionnelle, Functional Proteomics Platform, 34090 Montpellier, France
Department of Microbiology, Faculty of Public Health, Mahidol University, Bangkok 10400, Thailand
Institute of Technology, University of Tartu, 50090 Tartu, Estonia
Centre d’Immunologie et des Maladies Infectieuses, Inserm, U1135, Sorbonne Universités, UPMC, APHP Hôpital Pitié-Salpêtrière, 75013 Paris, France
Authors to whom correspondence should be addressed.
These authors have contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(7), 1695;
Received: 14 March 2019 / Revised: 23 March 2019 / Accepted: 3 April 2019 / Published: 5 April 2019
(This article belongs to the Special Issue Molecular Research on Emerging Mosquito-Transmitted RNA Viruses)
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. View Full-Text
Keywords: SAMHD1; arbovirus; Chikungunya; Zika; IFIT; SILAC SAMHD1; arbovirus; Chikungunya; Zika; IFIT; SILAC
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MDPI and ACS Style

Wichit, S.; Hamel, R.; Zanzoni, A.; Diop, F.; Cribier, A.; Talignani, L.; Diack, A.; Ferraris, P.; Liegeois, F.; Urbach, S.; Ekchariyawat, P.; Merits, A.; Yssel, H.; Benkirane, M.; Missé, D. SAMHD1 Enhances Chikungunya and Zika Virus Replication in Human Skin Fibroblasts. Int. J. Mol. Sci. 2019, 20, 1695.

AMA Style

Wichit S, Hamel R, Zanzoni A, Diop F, Cribier A, Talignani L, Diack A, Ferraris P, Liegeois F, Urbach S, Ekchariyawat P, Merits A, Yssel H, Benkirane M, Missé D. SAMHD1 Enhances Chikungunya and Zika Virus Replication in Human Skin Fibroblasts. International Journal of Molecular Sciences. 2019; 20(7):1695.

Chicago/Turabian Style

Wichit, Sineewanlaya, Rodolphe Hamel, Andreas Zanzoni, Fodé Diop, Alexandra Cribier, Loïc Talignani, Abibatou Diack, Pauline Ferraris, Florian Liegeois, Serge Urbach, Peeraya Ekchariyawat, Andres Merits, Hans Yssel, Monsef Benkirane, and Dorothée Missé. 2019. "SAMHD1 Enhances Chikungunya and Zika Virus Replication in Human Skin Fibroblasts" International Journal of Molecular Sciences 20, no. 7: 1695.

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