Cell culture-derived HCV cannot infect synovial fibroblasts

Area of Science:

• Virology
• Immunology
• Rheumatology

Background:

• Hepatitis C virus (HCV) infects 170 million globally, with 45 million experiencing arthropathy.
• The cause of HCV-related arthropathy remains unclear, with possibilities including direct viral infection or immune responses.

Purpose of the Study:

• To investigate the susceptibility of primary synovial fibroblasts to hepatitis C virus (HCV) infection and replication.
• To determine if synovial fibroblasts can support HCV propagation in vitro.

Main Methods:

• Primary human osteoarthritis synovial fibroblasts (OASF) and rheumatoid arthritis synovial fibroblasts (RASF) were analyzed for HCV receptor expression (CD81).
• Cells were tested for permissiveness to HCV infection using pseudotyped HCV particles.
• HCV replication capacity was assessed by transfecting cells with an HCV subgenomic replicon encoding a luciferase reporter.

Main Results:

• Synovial fibroblasts (OASF and RASF) expressed limited levels of the critical HCV receptor CD81.
• Pseudotyped HCV particles could not infect OASF and RASF.
• OASF and RASF did not support HCV replication, potentially due to low miR-122 expression.

Conclusions:

• Primary human synovial fibroblasts do not support hepatitis C virus (HCV) propagation in vitro.
• HCV-related arthropathy is unlikely to result from direct infection of synovial fibroblasts.