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Title: Human keratinocytes restrict chikungunya virus replication at a post-fusion step

Transmission of chikungunya virus (CHIKV) to humans is initiated by puncture of the skin by a blood-feeding Aedes mosquito. Despite the growing knowledge accumulated on CHIKV, the interplay between skin cells and CHIKV following inoculation still remains unclear. In this study we questioned the behavior of human keratinocytes, the predominant cell population in the skin, following viral challenge. We report that CHIKV rapidly elicits an innate immune response in these cells leading to the enhanced transcription of type I/II and type III interferon genes. Concomitantly, we show that despite viral particles internalization into Rab5-positive endosomes and efficient fusion of virus and cell membranes, keratinocytes poorly replicate CHIKV as attested by absence of nonstructural proteins and genomic RNA synthesis. Accordingly, human keratinocytes behave as an antiviral defense against CHIKV infection rather than as a primary targets for initial replication. This picture significantly differs from that reported for Dengue and West Nile mosquito-borne viruses. - Highlights: • Human keratinocytes support endocytosis of CHIKV and fusion of viral membranes. • CHIKV replication is blocked at a post entry step in these cells. • Infection upregulates type-I, –II and –III IFN genes expression. • Keratinocytes behave as immune sentinels against CHIKV.
Authors:
 [1] ;  [2] ;  [1] ;  [2] ;  [3] ;  [4] ;  [1] ;  [5] ;
  1. Centre d'étude d’agents Pathogènes et Biotechnologies pour la Santé, CPBS CNRS- UMR5236/UM1/UM2, Montpellier (France)
  2. Laboratoire Maladies Infectieuses et Vecteurs: Ecologie, Génétique, Evolution, Contrôle, UMR 5290 CNRS/IRD/UM1, Montpellier (France)
  3. INSERM U1058, UM1, CHU Montpellier (France)
  4. Blood Systems Research Institute, San Francisco, CA 94118 (United States)
  5. Unité Interactions Moléculaires Flavivirus-Hôtes, Institut Pasteur, Paris (France)
Publication Date:
OSTI Identifier:
22470147
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 476; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BLOOD; CELL MEMBRANES; FEEDING; GENES; HUMAN POPULATIONS; IMMUNITY; INOCULATION; INTERFERON; MOSQUITOES; PARTICLES; RNA; SKIN; SUPPORTS; SYNTHESIS; TRANSCRIPTION; VIRUSES