?Dissimilar expression of multidrug resistance mdr1 and bcrp by the replication of hepatitis C virus: role of the non structural 5A protein.?

RIVERO C, ROSSO N, CUESTAS ML, GENTILE E, TIRIBELLI C, OUBIÑA J, MATHET, V.

JOURNAL OF VIRAL HEPATITIS.

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2012

1352-0504

The hepatitis C virus (HCV) is a major cause of chronic liver disease. The non-structural 5A (NS5A) protein interferes with the response to interferon and appears to perform a crucial role in viral replication. Multidrug resistance is generally accepted as an important cause of treatment failure in patients with neoplastic or infectious diseases, playing a critical role in detoxification processes. In the present study, we investigated the effect of HCV replication and the nonstructural 5A (NS5A) protein on the expression of several ATP-dependent transport proteins, all members of the ABC super family. Comparative quantitative real time polymerase chain reaction (qPCR) was carried out for mdr1 and bcrp mRNAs in both Huh7cells expressing NS5A at different times post-transfection and HCV replicon systems (full length and subgenomic). A dose-dependent down-regulation of mdr1 expression was documented in Huh7 cells when the NS5A protein was expressed, as well as in the replicon systems. In contrast a significant increase of bcrp expression in both HCV replicons was recorded. These results warrant further in vivo studies in HCV patients with cholestasis and/or patients that are refractive to the pharmacotherapy due to the activity of these pumps.