SAMHD1 Enhances Chikungunya and Zika Virus Replication in Human Skin Fibroblasts

SAMHD1 Enhances Chikungunya and Zika Virus Replication in Human Skin Fibroblasts

April 06, 2019 0 Comments

IJMS | Free Full-Text | SAMHD1 Enhances Chikungunya and Zika Virus Replication in Human Skin Fibroblasts Next Article in Journal Low Serum Melatonin Levels Prior to Liver Transplantation in Patients with Hepatocellular Carcinoma are Associated with Lower Survival after Liver Transplantation Previous Article in Journal Regulation of Proliferation, Differentiation and Functions of Osteoblasts by Runx2 Previous Article in Special Issue A Viperin Mutant Bearing the K358R Substitution Lost its Anti-ZIKA Virus Activity Choose your preferred view mode Please select whether you prefer to view the MDPI pages with a view tailored for mobile displays or to view the MDPI pages in the normal scrollable desktop version. This selection will be stored into your cookies and used automatically in next visits. You can also change the view style at any point from the main header when using the pages with your mobile device. 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J. Mol. Sci. 2019, 20(7), 1695; https://doi.org/10.3390/ijms20071695 (registering DOI) SAMHD1 Enhances Chikungunya and Zika Virus Replication in Human Skin Fibroblasts Sineewanlaya Wichit1,* ,Rodolphe Hamel2,†,Andreas Zanzoni3,† ,Fodé Diop2,Alexandra Cribier4,Loïc Talignani2,Abibatou Diack2,Pauline Ferraris2,Florian Liegeois2 ,Serge Urbach5,Peeraya Ekchariyawat6,Andres Merits7,Hans Yssel8 ,Monsef Benkirane4 andDorothée Missé2,* 1 Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Nakhon Pathom 73170, Thailand 2 Laboratoire MIVEGEC, UMR 224 IRD/CNRS/UM1, 34394 Montpellier, France 3 Aix-Marseille Université, Inserm, TAGC UMR S1090, 13288 Marseille, France 4 Institut de Génétique Humaine, CNRS-Université de Montpellier, UMR 9002, 34090 Montpellier, France 5 Institut de Génétique Fonctionnelle, Functional Proteomics Platform, 34090 Montpellier, France 6 Department of Microbiology, Faculty of Public Health, Mahidol University, Bangkok 10400, Thailand 7 Institute of Technology, University of Tartu, 50090 Tartu, Estonia 8 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. 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) Full-Text   |   PDF[3554 KB, uploaded 5 April 2019]   |  Figures Abstract 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 ▼ Figures Figure 1 This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0). Supplementary materials Supplementary File 1: ZIP-Document(ZIP, 1917 KB) Externally hosted supplementary file 1 Link: https://www.mdpi.com/xxx/s1 Description: Table_ S1_SILAC analysis raw data of CHIKV-infected cells.xls Table_ S2_SILAC analysis raw data of ZIKV-infected cells.xls Table_ S3_Functional annotation of CHIKV- and ZIKV-infected cells.xls Table_ S4_Primers and probes for viral detection used in this study.doc Share & Cite This Article 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. Show more citation formats Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here. Article Metrics Article metric data becomes available approximately 24 hours after publication online. Article Access Statistics Abstract views Pdf views Html views 1 [Return to top] Submit to IJMS Review for IJMS Edit a Special Issue Int. J. Mol. Sci. 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