pH-dependent entry of Chikungunya virus into Aedes albopictus cells
Autor(es): Gay Bernard, Bernard Eric, Solignat Maxime, Chazal Nathalie, Devaux Christian, Briant Laurence
Resumo: The chikungunya virus (CHIKV) recently caused explosive outbreaks in Indian Ocean isl-s - India. During these episodes, the virus was mainly spread to humans through the bite of the mosquito Aedes albopictus. Concomitantly to the description of symptoms of an unexpected severity in infants - elderly patients, a viral genome microevolution has been highlighted, in particular consisting in the acquisition of an A226V mutation in the gene encoding envelope glycoprotein E1, which was later found to confer an increased fitness for A. albopictus. We previously decrypted the entry pathway used by CHIKV to infect human epithelial cells - showed that these mechanisms are modulated by the E1-A226V mutation. In this report we investigated the conditions for CHIKV entry into mosquito cells - we assessed the consequence of E1 gene mutation on these parameters. Our main findings indicate that CHIKV infection of A. albopictus cell lines is sensitive to Bafilomycin A1 - chloroquine - to membrane cholesterol depletion. The E1-226V mutated LR-OPY1 isolate collected during the 2005 outbreak in La Réunion replicated more efficiently than the 37997 African reference strain in C6/36 cells. Moreover, the LR-OPY1 strain displayed greater membrane cholesterol dependence - was more sensitive to inhibition of endosomal pH acidification. Finally, using electron microscopy, we imaged CHIKV entry into C6/36 cells. Our data support that CHIKV is endocyted into A. albopictus cells - requires membrane cholesterol as well as a low-pH environment for entry. These features are modulated in some extent by the A226V mutation in the E1 gene of the LR-OPY1 isolate. Altogether, our data provide information regarding the pathways used by CHIKV to infect A. albopictus cells.
Palavras-Chave: Chikungunya virus; Aedes albopictus; Viral entry; Cholesterol; Endosomal pH; Endocytosis
Imprenta: Infection, Genetics and Evolution, v. 12, n. 6, p. 1275-1281, 2012
Identificador do objeto digital: 10.1016/j.meegid.2012.02.003
Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - Genome ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya Virus - Virus ; Chikungunya virus - Public health
Data de publicação: 2012
