Infection of Human Liver Myofibroblasts by Hepatitis C Virus: A Direct Mechanism of Liver Fibrosis in Hepatitis C.
Chronic hepatitis C is a major cause of liver fibrosis and cirrhosis. It is generally accepted that inflammation that occurs in response to hepatocyte infection by the hepatitis C virus (HCV) is the main mechanism that triggers myofibroblast differentiation and stimulation in chronic hepatitis C. Th...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4516308?pdf=render |
| _version_ | 1828879103969722368 |
|---|---|
| author | Lynda Aoudjehane Grégoire Bisch Olivier Scatton Christelle Granier Jesintha Gaston Chantal Housset Philippe Roingeard François-Loïc Cosset Fabiano Perdigao Pierre Balladur Takaji Wakita Yvon Calmus Filomena Conti |
| author_facet | Lynda Aoudjehane Grégoire Bisch Olivier Scatton Christelle Granier Jesintha Gaston Chantal Housset Philippe Roingeard François-Loïc Cosset Fabiano Perdigao Pierre Balladur Takaji Wakita Yvon Calmus Filomena Conti |
| author_sort | Lynda Aoudjehane |
| collection | DOAJ |
| description | Chronic hepatitis C is a major cause of liver fibrosis and cirrhosis. It is generally accepted that inflammation that occurs in response to hepatocyte infection by the hepatitis C virus (HCV) is the main mechanism that triggers myofibroblast differentiation and stimulation in chronic hepatitis C. The aim of this study was to determine if HCV might infect human liver myofibroblasts (HLMF) and directly stimulate their fibrogenic activities.We evaluated the expression of the viral entry receptors, levels of HCV-RNA and HCV-protein and the expression of fibrosis markers in HLMF by using quantitative PCR, western blot and immunofluorescence analyses. Pseudoparticles (HCVpp) and cell culture-derived HCV (HCVcc) were used to study the ability of HLMF to support viral entry, replication and fibrosis induction.We showed that HLMF expressed all known molecules of the HCV receptor complex, i.e. CD81, LDL-R, scavenger receptor-BI, claudin-1 and occludin. These cells were also permissive to HCVpp entry. Inoculation with HCVcc caused short-term infection of these cells, as shown by their content in positive- and negative-strand HCV RNA, in core and NS3 viral proteins, and by their release of core protein levels in the culture supernatants. HCV infection stimulated myofibroblastic differentiation, proliferation and collagen production in these cells. In addition, evidence of in vivo infection was provided by the detection of positive- and negative-strand HCV RNA in preparations of HLMF obtained from HCV-infected patients.These findings indicate that HCV infection of HLMF can occur and trigger extracellular matrix overproduction, thereby contributing to the development of HCV-related liver fibrosis. |
| first_indexed | 2024-12-13T09:20:14Z |
| format | Article |
| id | doaj.art-c3c91e32fd9d4b0d8bf4b8df03224cbe |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T09:20:14Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c3c91e32fd9d4b0d8bf4b8df03224cbe2022-12-21T23:52:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01107e013414110.1371/journal.pone.0134141Infection of Human Liver Myofibroblasts by Hepatitis C Virus: A Direct Mechanism of Liver Fibrosis in Hepatitis C.Lynda AoudjehaneGrégoire BischOlivier ScattonChristelle GranierJesintha GastonChantal HoussetPhilippe RoingeardFrançois-Loïc CossetFabiano PerdigaoPierre BalladurTakaji WakitaYvon CalmusFilomena ContiChronic hepatitis C is a major cause of liver fibrosis and cirrhosis. It is generally accepted that inflammation that occurs in response to hepatocyte infection by the hepatitis C virus (HCV) is the main mechanism that triggers myofibroblast differentiation and stimulation in chronic hepatitis C. The aim of this study was to determine if HCV might infect human liver myofibroblasts (HLMF) and directly stimulate their fibrogenic activities.We evaluated the expression of the viral entry receptors, levels of HCV-RNA and HCV-protein and the expression of fibrosis markers in HLMF by using quantitative PCR, western blot and immunofluorescence analyses. Pseudoparticles (HCVpp) and cell culture-derived HCV (HCVcc) were used to study the ability of HLMF to support viral entry, replication and fibrosis induction.We showed that HLMF expressed all known molecules of the HCV receptor complex, i.e. CD81, LDL-R, scavenger receptor-BI, claudin-1 and occludin. These cells were also permissive to HCVpp entry. Inoculation with HCVcc caused short-term infection of these cells, as shown by their content in positive- and negative-strand HCV RNA, in core and NS3 viral proteins, and by their release of core protein levels in the culture supernatants. HCV infection stimulated myofibroblastic differentiation, proliferation and collagen production in these cells. In addition, evidence of in vivo infection was provided by the detection of positive- and negative-strand HCV RNA in preparations of HLMF obtained from HCV-infected patients.These findings indicate that HCV infection of HLMF can occur and trigger extracellular matrix overproduction, thereby contributing to the development of HCV-related liver fibrosis.http://europepmc.org/articles/PMC4516308?pdf=render |
| spellingShingle | Lynda Aoudjehane Grégoire Bisch Olivier Scatton Christelle Granier Jesintha Gaston Chantal Housset Philippe Roingeard François-Loïc Cosset Fabiano Perdigao Pierre Balladur Takaji Wakita Yvon Calmus Filomena Conti Infection of Human Liver Myofibroblasts by Hepatitis C Virus: A Direct Mechanism of Liver Fibrosis in Hepatitis C. PLoS ONE |
| title | Infection of Human Liver Myofibroblasts by Hepatitis C Virus: A Direct Mechanism of Liver Fibrosis in Hepatitis C. |
| title_full | Infection of Human Liver Myofibroblasts by Hepatitis C Virus: A Direct Mechanism of Liver Fibrosis in Hepatitis C. |
| title_fullStr | Infection of Human Liver Myofibroblasts by Hepatitis C Virus: A Direct Mechanism of Liver Fibrosis in Hepatitis C. |
| title_full_unstemmed | Infection of Human Liver Myofibroblasts by Hepatitis C Virus: A Direct Mechanism of Liver Fibrosis in Hepatitis C. |
| title_short | Infection of Human Liver Myofibroblasts by Hepatitis C Virus: A Direct Mechanism of Liver Fibrosis in Hepatitis C. |
| title_sort | infection of human liver myofibroblasts by hepatitis c virus a direct mechanism of liver fibrosis in hepatitis c |
| url | http://europepmc.org/articles/PMC4516308?pdf=render |
| work_keys_str_mv | AT lyndaaoudjehane infectionofhumanlivermyofibroblastsbyhepatitiscvirusadirectmechanismofliverfibrosisinhepatitisc AT gregoirebisch infectionofhumanlivermyofibroblastsbyhepatitiscvirusadirectmechanismofliverfibrosisinhepatitisc AT olivierscatton infectionofhumanlivermyofibroblastsbyhepatitiscvirusadirectmechanismofliverfibrosisinhepatitisc AT christellegranier infectionofhumanlivermyofibroblastsbyhepatitiscvirusadirectmechanismofliverfibrosisinhepatitisc AT jesinthagaston infectionofhumanlivermyofibroblastsbyhepatitiscvirusadirectmechanismofliverfibrosisinhepatitisc AT chantalhousset infectionofhumanlivermyofibroblastsbyhepatitiscvirusadirectmechanismofliverfibrosisinhepatitisc AT philipperoingeard infectionofhumanlivermyofibroblastsbyhepatitiscvirusadirectmechanismofliverfibrosisinhepatitisc AT francoisloiccosset infectionofhumanlivermyofibroblastsbyhepatitiscvirusadirectmechanismofliverfibrosisinhepatitisc AT fabianoperdigao infectionofhumanlivermyofibroblastsbyhepatitiscvirusadirectmechanismofliverfibrosisinhepatitisc AT pierreballadur infectionofhumanlivermyofibroblastsbyhepatitiscvirusadirectmechanismofliverfibrosisinhepatitisc AT takajiwakita infectionofhumanlivermyofibroblastsbyhepatitiscvirusadirectmechanismofliverfibrosisinhepatitisc AT yvoncalmus infectionofhumanlivermyofibroblastsbyhepatitiscvirusadirectmechanismofliverfibrosisinhepatitisc AT filomenaconti infectionofhumanlivermyofibroblastsbyhepatitiscvirusadirectmechanismofliverfibrosisinhepatitisc |