Abstract
Worldwide 170 million individuals are infected with hepatitis C virus (HCV), up to 45 million of whom are affected by arthropathy. It is unclear whether this is due to viral infection of synovial cells or immune-mediated mechanisms. We tested the capacity of primary synovial fibroblasts to support HCV propagation. Out of the four critical HCV receptors, only CD81 was expressed to any significant extent in OASF and RASF. Consistent with this, pseudotyped HCV particles were unable to infect these cells. Permissiveness for HCV replication was investigated by transfecting cells with a subgenomic replicon of HCV encoding a luciferase reporter. OASF and RASF did not support replication of HCV, possibly due to low expression levels of miR-122. In conclusion, primary human synovial fibroblasts are unable to support propagation of HCV in vitro. HCV-related arthropathy is unlikely due to direct infection of these cells.
Highlights
To explore permissiveness of OASF and RASF for hepatitis C virus (HCV), we first explored the expression of the four critical HCV cell entry factors CD81, scavenger receptor class B type I (SR-BI), CLDN1 and OCLN24
CD81 mRNA was expressed in OASF and RASF at higher levels than in Huh-7.5 cells (Fig. 1a), whereas OCLN and SR-BI transcripts were expressed at lower levels in OASF and RASF than in Huh-7.5 cells
We examined the permissiveness of human primary OASF and RASF cells for HCV cell entry and RNA replication using a combination of mRNA and protein expression analyses as well as HCV infection and replication assays
Summary
Attempts to detect HCV in the synovial fluid of a small number of patients suffering from both HCV infection and arthritis have mostly yielded negative results[16]. Due to the non-erosive nature of HAA, surgically removed joint tissue usually does not become available, and synovial biopsies are usually not obtained from patients being evaluated for HAA. A systematic search for HCV in synovial tissue from patients with HAA has not been possible and is unlikely to take place in the foreseeable future. As a first non-invasive step toward testing the hypothesis that HAA may be due to infection of resident synovial cells, we have studied the capacity of OA synovial fibroblasts from patients with RA (RASF) and OA (OASF) to support HCV entry and replication
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
