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Restricted mumps virus infection of cells derived from normal human joint tissue
1Division of Medical Microbiology, University of British Columbia, Vancouver, Canada.
Abstract:
Mumps virus (MuV) is known to be associated with acute arthritis and may also have a role in chronic inflammatory joint disease. The mechanism of induction of joint inflammation is not known but may be associated with direct invasion of joint tissue. To investigate the possibility of persistent intra-articular infection, the interaction of MuV with primary cells from normal human joint tissue was examined. These mixed cultures of synovial membrane cells and chondrocytes were found to be semi-permissive to the virus; only a small proportion of cells (5 to 20%) were infected and produced low titres of progeny virions. In addition, little viral antigen was detected on the cell surface relative to that found on Vero cells. This restricted infection of synovial membrane cells was related to a severely decreased synthesis of the viral glycoproteins, fusion and haemagglutinin-neuraminidase, and the membrane protein in comparison to the levels found in Vero cells. Persistent infections were readily established and could be maintained for 2 to 3 months. During the first month, the infection remained highly focal and supernatant viral titres were low. Thereafter both the percentage of infected cells and viral titres increased until finally the cultures were killed. No evidence was obtained for the generation of temperature-sensitive mutants or defective interfering particles during long-term infection, but the persistent virus derived from the cultures gave cloudy plaques and induced no fusion in Vero cells until passaged. This study has shown that human synovial tissue cells have the intrinsic ability to support MuV replication and persistence which may be important in the pathogenesis of mumps arthritis.
Insights
Mumps virus (MuV) can infect human joint cells, leading to persistent infections. This viral persistence in synovial tissue may contribute to the development of mumps arthritis.
Area of Science:
- Virology
- Immunology
- Rheumatology
Background:
- Mumps virus (MuV) is linked to acute arthritis and potentially chronic inflammatory joint diseases.
- The precise mechanism of joint inflammation induction by MuV remains unclear, possibly involving direct tissue invasion.
Purpose of the Study:
- To investigate the potential for persistent intra-articular infection by examining MuV interaction with primary human joint cells.
- To elucidate the role of MuV replication and persistence in synovial tissue in the pathogenesis of mumps arthritis.
Main Methods:
- Primary cultures of human synovial membrane cells and chondrocytes were exposed to MuV.
- Viral replication, antigen expression, and glycoprotein synthesis were analyzed in infected cells compared to control Vero cells.
- Long-term infection dynamics, including viral titers and cell viability, were monitored over several months.
Main Results:
- Human joint cells supported semi-permissive MuV replication, with 5-20% infection and low progeny virion production.
- Infected cells exhibited significantly decreased synthesis of viral glycoproteins (fusion and hemagglutinin-neuraminidase) and membrane protein.
- Persistent MuV infections were established for up to 3 months, initially focal with low viral titers, progressing to increased infection and cell death.
Conclusions:
- Human synovial tissue cells possess the intrinsic capacity to support MuV replication and establish persistent infections.
- This ability of MuV to persist within joint tissues may play a significant role in the pathogenesis of mumps arthritis.