Dataset Information

SAMHD1 Enhances Chikungunya and Zika Virus Replication in Human Skin Fibroblasts.

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.

SUBMITTER: Wichit S

PROVIDER: S-EPMC6480247 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

SAMHD1 Enhances Chikungunya and Zika Virus Replication in Human Skin Fibroblasts.

Wichit Sineewanlaya S Hamel Rodolphe R Zanzoni Andreas A Diop Fodé F Cribier Alexandra A Talignani Loïc L Diack Abibatou A Ferraris Pauline P Liegeois Florian F Urbach Serge S Ekchariyawat Peeraya P Merits Andres A Yssel Hans H Benkirane Monsef M Missé Dorothée D

International journal of molecular sciences 20190405 7

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 tha ...[more]

PMID: 30959732

Similar Datasets

Project description:UnlabelledZika virus (ZIKV) is an emerging arbovirus of the Flaviviridae family, which includes dengue, West Nile, yellow fever, and Japanese encephalitis viruses, that causes a mosquito-borne disease transmitted by the Aedes genus, with recent outbreaks in the South Pacific. Here we examine the importance of human skin in the entry of ZIKV and its contribution to the induction of antiviral immune responses. We show that human dermal fibroblasts, epidermal keratinocytes, and immature dendritic cells are permissive to the most recent ZIKV isolate, responsible for the epidemic in French Polynesia. Several entry and/or adhesion factors, including DC-SIGN, AXL, Tyro3, and, to a lesser extent, TIM-1, permitted ZIKV entry, with a major role for the TAM receptor AXL. The ZIKV permissiveness of human skin fibroblasts was confirmed by the use of a neutralizing antibody and specific RNA silencing. ZIKV induced the transcription of Toll-like receptor 3 (TLR3), RIG-I, and MDA5, as well as several interferon-stimulated genes, including OAS2, ISG15, and MX1, characterized by strongly enhanced beta interferon gene expression. ZIKV was found to be sensitive to the antiviral effects of both type I and type II interferons. Finally, infection of skin fibroblasts resulted in the formation of autophagosomes, whose presence was associated with enhanced viral replication, as shown by the use of Torin 1, a chemical inducer of autophagy, and the specific autophagy inhibitor 3-methyladenine. The results presented herein permit us to gain further insight into the biology of ZIKV and to devise strategies aiming to interfere with the pathology caused by this emerging flavivirus.ImportanceZika virus (ZIKV) is an arbovirus belonging to the Flaviviridae family. Vector-mediated transmission of ZIKV is initiated when a blood-feeding female Aedes mosquito injects the virus into the skin of its mammalian host, followed by infection of permissive cells via specific receptors. Indeed, skin immune cells, including dermal fibroblasts, epidermal keratinocytes, and immature dendritic cells, were all found to be permissive to ZIKV infection. The results also show a major role for the phosphatidylserine receptor AXL as a ZIKV entry receptor and for cellular autophagy in enhancing ZIKV replication in permissive cells. ZIKV replication leads to activation of an antiviral innate immune response and the production of type I interferons in infected cells. Taken together, these results provide the first general insights into the interaction between ZIKV and its mammalian host.

Project description:Dengue viruses are the most important arboviral pathogens in the world, which have adapted to human transmission and replication over several hundred years and were initially recognized to cause outbreaks of clinical disease in tropical and subtropical countries by Aedes aegypti mosquitoes. Subsequent global expansion of dengue infection outbreaks has occurred, with millions of cases yearly, probably from a combination of factors including proliferation of international travel and trade, possibly global climate changes, adaptation of the vectors to new environment, and emergence of a new mosquito vector, Aedes albopictus. Chikungunya virus, also transmitted by Aedes mosquitoes, causes a very similar clinical disease but with more prominent arthralgia or arthritis and was originally described in Africa in the 1960s. After a quiescent period of several decades, it reemerged in Africa in 2004 and rapidly spread across the Indian Ocean to involve Asian countries and parts of Europe. However, the past 2 years have seen the emergence of chikungunya virus in the western hemisphere with major outbreaks in the Caribbean and the Americas. Similar to dengue virus, chikungunya virus has adapted to Ae. albopictus mosquitoes which can transmit the disease. Although dengue infection is a more deadly disease especially in young children, chikungunya infection can cause prolonged severe disability and occasionally rare fatalities from encephalitis. No specific treatment is available for either diseases, but development of an effective vaccine for dengue infection is in progress. Until 2007, Zika virus [also transmitted by Aedes species] was associated with only sporadic mild infections in Africa and Asia. In 2007, Zika virus for the first time caused an outbreak beyond Africa and Asia to the Yap Island in the Federated States of Micronesia. Since then Zika virus has spread to French Polynesia, New Caledonia, Cook Islands, and Easter Island in the southeastern Pacific Ocean [Chile] in 2014 and by 2015 to Brazil. By January 2016, it became evident that Zika virus had caused an explosive outbreak in the Americas and the Caribbean with over 30 countries affected. On February 1, 2016, the World Health Organization declared Zika outbreak a global public health emergency. Zika virus infection is most commonly asymptomatic, and 20% of patients may develop a mild viral disease, but of major concern is the reported association of microcephaly in infected pregnant women in Brazil. This chapter explores the history, epidemiology, pathogenesis, clinical features, treatment, and prevention of these rapidly emerging zoonoses.

Dataset Information

SAMHD1 Enhances Chikungunya and Zika Virus Replication in Human Skin Fibroblasts.

Publications

SAMHD1 Enhances Chikungunya and Zika Virus Replication in Human Skin Fibroblasts.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets