Related Experiment Videos
Coronavirus mouse hepatitis virus (MHV)-A59 causes a persistent, productive infection in primary glial cell cultures
E Lavi1, A Suzumura, M Hirayama
1Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia 19104.
Abstract:
MHV-A59 causes a chronic demyelinating disease in mice which is accompanied by persistence of viral genome in white matter. As part of the investigation into the mechanism of viral persistence, infection of glial cells, probable targets for chronic infection, was studied by the use of mixed glial, enriched oligodendrocyte and enriched astrocyte cultures. Following MHV-A59 infection in vitro, approximately 10% of oligodendrocytes and 30% of astrocytes expressed viral antigens in the absence of overt cytopathic effect. All cultures released infectious virus for the lifetime of the cultures, for at least 45 days in the case of mixed glial cultures. Cultures derived from previously infected mice were similar to those infected in vitro with respect to percentage of cells expressing viral antigen and levels of infectious virus produced. These results show (1) that glial cells are early sites of infection in vivo as well as sites of infection in vitro cultures, and (2) that glial cells support a non-lytic but productive infection in vitro and thus may contribute to viral persistence in vivo.
Insights
Murine hepatitis virus (MHV-A59) establishes persistent infections in mouse white matter. Glial cells, including oligodendrocytes and astrocytes, support non-lytic but productive viral replication, contributing to chronic demyelinating disease.
Area of Science:
- Neurovirology
- Immunology
- Cell Biology
Background:
- Murine hepatitis virus (MHV-A59) induces chronic demyelinating disease in mice.
- Viral genome persistence in white matter is a hallmark of MHV-A59 infection.
- Glial cells are potential targets for chronic viral infections.
Purpose of the Study:
- To investigate the role of glial cells in MHV-A59 viral persistence.
- To determine if glial cells support productive MHV-A59 infection in vitro.
- To understand the contribution of glial cells to chronic demyelinating disease.
Main Methods:
- Infection of mixed glial, enriched oligodendrocyte, and enriched astrocyte cultures with MHV-A59 in vitro.
- Detection of viral antigens in glial cells via immunofluorescence.
- Quantification of infectious virus release from cultures.
- Comparison of in vitro infection with cultures derived from infected mice.
Main Results:
- Oligodendrocytes (10%) and astrocytes (30%) expressed viral antigens post-MHV-A59 infection without significant cell death.
- Infectious virus was continuously released from all glial cultures for at least 45 days.
- Glial cultures from previously infected mice mirrored in vitro infection patterns.
- Glial cells serve as early sites of MHV-A59 infection in vivo and in vitro.
Conclusions:
- Glial cells support a non-lytic but productive MHV-A59 infection.
- Glial cells are likely crucial for the persistence of MHV-A59 in the central nervous system.
- These findings elucidate mechanisms contributing to MHV-A59-induced chronic demyelinating disease.