Hepatitis C virus (HCV) protein expression enhances hepatic fibrosis in HCV transgenic mice exposed to a fibrogenic agent

Chouteau, Philippe; Defer, Nicole; Florimond, A.; Caldéraro, Julien; Higgs, Martin R.; Gaudin, Aurore; Mérour, Emilie; Dhumeaux, Daniel; Lerat, Hervé; Pawlotsky, Jean‐Michel

doi:10.1016/j.jhep.2012.04.019

Cited by 19 publications

(12 citation statements)

References 40 publications

(51 reference statements)

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“…Thus, HCV infection of HSCs does not play a role in liver fibrosis. These results do not rule out a direct role of HCV infection of hepatocytes in the fibrogenic process as we recently suggested 17. Nevertheless, chronic inflammation in relation to the local immune response still appears to be the main trigger of liver fibrosis in patients with chronic hepatitis C.…”

Section: Discussioncontrasting

confidence: 63%

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Human hepatic stellate cells are not permissive for hepatitis C virus entry and replication

Florimond

Chouteau

Bruscella

et al. 2014

Gut

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Section: Discussioncontrasting

confidence: 63%

“…Cellular proteins were processed as previously described 17. Cultured cells were lysed in cold lysis buffer containing 1% NP40, 10% glycerol, 100 mM Tris pH8, 100 mM KCl, protease and phosphatase inhibitors.…”

Section: Methodsmentioning

confidence: 99%

Human hepatic stellate cells are not permissive for hepatitis C virus entry and replication

Florimond

Chouteau

Bruscella

et al. 2014

Gut

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“…ROS is a critical regulator of hepatic fibrosis progression [60], [61], [62], [63], [64], whose level is increased by ethanol metabolism and HCV infection [60], [65], [66], [67]. It is also reported that HIV-1 and HCV cooperatively promotes hepatic fibrogenesis by inducing ROS [13], [68], and therefore we investigated whether Nef is a responsible element in generation of ROS in the hepatocytes.…”

Section: Resultsmentioning

confidence: 99%

HIV-1 Nef Is Transferred from Expressing T Cells to Hepatocytic Cells through Conduits and Enhances HCV Replication

et al. 2014

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HIV-1 infection enhances HCV replication and as a consequence accelerates HCV-mediated hepatocellular carcinoma (HCC). However, the precise molecular mechanism by which this takes place is currently unknown. Our data showed that infectious HIV-1 failed to replicate in human hepatocytic cell lines. No discernible virus replication was observed, even when the cell lines transfected with HIV-1 proviral DNA were co-cultured with Jurkat T cells, indicating that the problem of liver deterioration in the co-infected patient is not due to the replication of HIV-1 in the hepatocytes of the HCV infected host. Instead, HIV-1 Nef protein was transferred from nef-expressing T cells to hepatocytic cells through conduits, wherein up to 16% (average 10%) of the cells harbored the transferred Nef, when the hepatocytic cells were co-cultured with nef-expressing Jurkat cells for 24 h. Further, Nef altered the size and numbers of lipid droplets (LD), and consistently up-regulated HCV replication by 1.5∼2.5 fold in the target subgenomic replicon cells, which is remarkable in relation to the initially indolent viral replication. Nef also dramatically augmented reactive oxygen species (ROS) production and enhanced ethanol-mediated up-regulation of HCV replication so as to accelerate HCC. Taken together, these data indicate that HIV-1 Nef is a critical element in accelerating progression of liver pathogenesis via enhancing HCV replication and coordinating modulation of key intra- and extra-cellular molecules for liver decay.

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“…HCV core protein promotes HSCs proliferation, while the NS3 protease is pro-inflammatory by inducing transforming growth factor beta (TGF-β) signaling and collagen production in hepatic cells 18, 19 . Transgenic mice expressing the full-length HCV open reading frame in hepatocytes contributes to the development of hepatic fibrosis in the presence of carbon tetrachloride 20 . HCV subgenome replicon cells release TGF-β1 and other unidentified factors to induce procollagen gene expression in HSCs 21 .…”

Section: Introductionmentioning

confidence: 99%

Activation of hepatic stellate cells by the ubiquitin C-terminal hydrolase 1 protein secreted from hepatitis C virus-infected hepatocytes

Cheng

Tseng

Liao

et al. 2017

Sci Rep

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Hepatitis C virus (HCV) infection of hepatocytes promotes liver fibrosis by activation of hepatic stellate cells (HSCs) and excessive deposition of extracellular matrix in liver tissue. Whether or not host factors released from the HCV-infected hepatocytes play role in HSCs activation is unclear. In this study, HSCs were activated by the conditioned medium derived from HCV replicon cells. Secretomic profiling of HCV replicon cells and the parental Huh7 cells revealed ubiquitin carboxy-terminal hydrolase L1 (UCHL1) as a novel secreted protein from HCV-infected hepatocytes. UCHL1 expression in hepatocytes was induced by HCV infection. UCHL1 was expressed in the liver and found in the plasma of patients with chronic hepatitis C. Molecular analysis by use of the anti-UCHL1 neutralization antibody and purified UCHL1 protein showed that secreted UCHL1 protein was bound to the cell surface of HSCs and activated JNK signaling leading to overexpression of alpha-smooth muscle actin and the activation of HSCs. These results provide further for understanding the underlying mechanism in HCV-mediated hepatic fibrogenesis.

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Hepatitis C virus (HCV) protein expression enhances hepatic fibrosis in HCV transgenic mice exposed to a fibrogenic agent

Abstract: electronic word count: 244 *Manuscript

Cited by 19 publications

References 40 publications

Human hepatic stellate cells are not permissive for hepatitis C virus entry and replication

Human hepatic stellate cells are not permissive for hepatitis C virus entry and replication

HIV-1 Nef Is Transferred from Expressing T Cells to Hepatocytic Cells through Conduits and Enhances HCV Replication

Activation of hepatic stellate cells by the ubiquitin C-terminal hydrolase 1 protein secreted from hepatitis C virus-infected hepatocytes

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