Autor(es): Bernard Eric, Solignat Maxime, Gay Bernard, Chazal Nathalie, Higgs Stephen, Devaux Christian, Briant Laurence

Resumo: The replicative cycle of chikungunya virus (CHIKV), an alphavirus that recently re-emerged in India - in Indian Ocean area, remains mostly unknown. The aim of the present study was to investigate the intracellular trafficking pathway(s) hijacked by CHIKV to enter mammalian cells. Entry pathways were investigated using a variety of pharmacological inhibitors or overexpression of dominant negative forms of proteins perturbating cellular endocytosis. We found that CHIKV infection of HEK293T mammalian cells is independent of clathrin heavy chain -- dependent of functional Eps15, - requires integrity of Rab5-, but not Rab7-positive endosomal compartment. Cytoskeleton integrity is crucial as cytochalasin D - nocodazole significantly reduced infection of the cells. Finally, both methyl beta-cyclodextrin - lysomotropic agents impaired CHIKV infection, supporting that a cholesterol-, pH-dependent step is required to achieve productive infection. Interestingly, differential sensitivity to lysomotropic agents was observed between the prototypal 37997 African strain of CHIKV - the LR-OPY1 virus isolated from the recent outbreak in Reunion Isl-. Together our data indicate that CHIKV entry in its target cells is essentially mediated by clathrin-independent, Eps15-dependent endocytosis. Despite that this property is shared by the prototypal 37997 African strain of CHIKV - the LR-OPY1 virus isolated from the recent outbreak in La Réunion Isl-, differential sensitivity to lysomotropic agents may support that the LR-OPY1 strain has acquired specific entry mechanisms.

Imprenta: PloS One, v. 5, n. 7, p. e11479, 2010

Identificador do objeto digital: 10.1371/journal.pone.0011479

Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - RNA ; Chikungunya Virus - Virus

Data de publicação: 2010