scholarly journals Hepatitis C virus NS 5A drives a PTEN ‐ PI 3K/Akt feedback loop to support cell survival

2014 ◽  
Vol 35 (6) ◽  
pp. 1682-1691 ◽  
Author(s):  
Du Cheng ◽  
Leiliang Zhang ◽  
Guangbo Yang ◽  
Lei Zhao ◽  
Feng Peng ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Cell Survival ◽  
Feedback Loop ◽  
Support Cell

scholarly journals Activation of the N-Ras–PI3K–Akt-mTOR Pathway by Hepatitis C Virus: Control of Cell Survival and Viral Replication

2005 ◽  
Vol 79 (14) ◽  
pp. 8742-8749 ◽  
Author(s):  
Petra Mannová ◽  
Laura Beretta
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Cell Survival ◽  
Akt Pathway ◽  
Serum Starvation ◽  
Two Dimensional Gel Electrophoresis ◽  
Pi3k Inhibitor Ly294002 ◽  
Downstream Target ◽  
Huh7 Cells ◽  
In Cells

ABSTRACT The hepatitis C virus (HCV) replication complex is localized within detergent-resistant membranes or lipid rafts. We analyzed the protein contents of detergent-resistant fractions isolated from Huh7 cells expressing a self-replicating full-length HCV-1b genome. Using two-dimensional gel electrophoresis followed by mass spectrometry, we identified N-Ras as one of the proteins in which expression was increased in the detergent-resistant fractions from HCV genomic replicon clones compared to control cells. N-Ras is an activator of the phosphatidylinositol-3-kinase (PI3K)-Akt pathway. We found that the activities of PI3K and Akt, as well as the activity of their downstream target, mTOR, in the HCV-replicating cells were increased. Both PI3K-Akt- and mTOR-dependent pathways have been shown to promote cell survival. In agreement with this, HCV replicon cells were resistant to serum starvation-induced apoptosis. We also characterized the role of this pathway in HCV replication. Reduction of N-Ras expression by transfection of N-Ras small interfering RNA (siRNA) resulted in increased replication of HCV. We observed a similar increase in HCV replication in cells treated with the PI3K inhibitor LY294002 and in cells transfected with mTOR siRNA. Taken together, these data suggest that increased N-Ras levels in subcellular sites of HCV replication and stimulation of the prosurvival PI3K-Akt pathway and mTOR by HCV not only protect cells against apoptosis but also contribute to the maintenance of steady-state levels of HCV replication. These effects may contribute to the establishment of persistent infection by HCV.

HEPATITIS C VIRUS INFECTION (AND ADDITIONAL NEOPLASMS) AMONG MARGINAL ZONE LYMPHOMAS

1997 ◽  
Vol 96 (2) ◽  
pp. 427-428 ◽  
Author(s):  
FREDERICO SILVESTRI ◽  
GIOVANNI BARILLARI ◽  
RENATO FANIN ◽  
FLAVIA SALMASO ◽  
LAURA INFANTI ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Marginal Zone ◽  
Hepatitis C Virus Infection
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