title: Human keratinocytes restrict chikungunya virus replication at a post-fusion step.
abstract: 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.
authors.affiliation: Centre d׳étude d'agents Pathogènes et Biotechnologies pour la Santé, CPBS CNRS- UMR5236/UM1/UM2, Montpellier, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Bernard
authors.affiliation: Laboratoire Maladies Infectieuses et Vecteurs: Ecologie, Génétique, Evolution, Contrôle, UMR 5290 CNRS/IRD/UM1, Montpellier, France.
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Hamel
authors.affiliation: Centre d׳étude d'agents Pathogènes et Biotechnologies pour la Santé, CPBS CNRS- UMR5236/UM1/UM2, Montpellier, France.
authors.forename: Aymeric
authors.initials: A
authors.lastname: Neyret
authors.affiliation: Laboratoire Maladies Infectieuses et Vecteurs: Ecologie, Génétique, Evolution, Contrôle, UMR 5290 CNRS/IRD/UM1, Montpellier, France.
authors.forename: Peeraya
authors.initials: P
authors.lastname: Ekchariyawat
authors.affiliation: INSERM U1058, UM1, CHU Montpellier, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Molès
authors.affiliation: Blood Systems Research Institute, San Francisco, CA 94118, USA.
authors.forename: Graham
authors.initials: G
authors.lastname: Simmons
authors.affiliation: Centre d׳étude d'agents Pathogènes et Biotechnologies pour la Santé, CPBS CNRS- UMR5236/UM1/UM2, Montpellier, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chazal
authors.affiliation: Unité Interactions Moléculaires Flavivirus-Hôtes, Institut Pasteur, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Desprès
authors.affiliation: Laboratoire Maladies Infectieuses et Vecteurs: Ecologie, Génétique, Evolution, Contrôle, UMR 5290 CNRS/IRD/UM1, Montpellier, France.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Missé
authors.affiliation: Centre d׳étude d'agents Pathogènes et Biotechnologies pour la Santé, CPBS CNRS- UMR5236/UM1/UM2, Montpellier, France. Electronic address: laurence.briant@cpbs.cnrs.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Briant
mesh_terms: D000330:Aedes; D000818:Animals; D002478:Cells, Cultured; D065632:Chikungunya Fever / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D002646:Chikungunya virus / Q000235:genetics / Q000502:physiology*; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D007372:Interferons / Q000235:genetics / Q000276:immunology; D015603:Keratinocytes / Q000276:immunology* / Q000821:virology*; D053586:Virus Internalization; D014779:Virus Replication
chemical_list: D007372:Interferons
keywords: Chikungunya; Innate immunity; Keratinocytes; Replication