Related Experiment Videos
Coronavirus induction of class I major histocompatibility complex expression in murine astrocytes is virus strain
W Gilmore1, J Correale, L P Weiner
1Department of Neurology, University of Southern California School of Medicine, Los Angeles 90033.
Abstract:
Neurotropic strains of mouse hepatitis viruses (MHV) such as MHV-A59 (A59) and MHV-4 (JHMV) cause acute and chronic encephalomyelitis and demyelination in susceptible strains of mice and rats. They are widely used as models of human demyelinating diseases such as multiple sclerosis (MS), in which immune mechanisms are thought to participate in the development of lesions in the central nervous system (CNS). The effects of MHV infection on target cell functions in the CNS are not well understood, but A59 has been shown to induce the expression of MHC class I molecules in glial cells after in vivo and in vitro infection. Changes in class I expression in infected cells may contribute to the immunopathogenesis of MHV infection in the CNS. In this communication, a large panel of MHV strains was tested for their ability to stimulate class I expression in primary astrocytes in vitro. The data show that the more hepatotropic strains, such as MHV-A59, MHV-1, MHV-2, MHV-3, MHV-D, MHV-K, and MHV-NuU, were potent inducers of class I expression in astrocytes during acute infection, measured by radioimmunoassay. The Kb molecule was preferentially expressed over Db. By contrast, JHMV and several viral strains derived from it did not stimulate the expression of class I molecules. Assays of virus infectivity indicated that the class I-inducing activity did not correlate with the ability of the individual viral strain to replicate in astrocytes. However, exposure of the viruses or the supernatants from infected astrocytes to ultraviolet light abolished the class I-inducing activity, indicating that infectious virus is required for class I expression. These data also suggest that class I expression was induced directly by virus infection, and not by the secretion of a soluble substance into the medium by infected astrocytes. Finally, analyses of A59/JHMV recombinant viral strains suggest that class I-inducing activity resides in one of the A59 structural genes.
Insights
Certain mouse hepatitis virus (MHV) strains, particularly hepatotropic ones like MHV-A59, strongly induce MHC class I expression in astrocytes, crucial for understanding central nervous system (CNS) demyelinating diseases.
Area of Science:
- Neurovirology
- Immunology
- Central Nervous System (CNS) Research
Background:
- Neurotropic mouse hepatitis viruses (MHV) are models for human demyelinating diseases like multiple sclerosis (MS).
- MHV infection impacts CNS cell function, with MHV-A59 known to upregulate MHC class I in glial cells.
- Understanding MHC class I modulation is key to MHV immunopathogenesis in the CNS.
Purpose of the Study:
- To investigate the ability of various MHV strains to induce MHC class I expression in primary astrocytes.
- To determine if MHV strain tropism correlates with MHC class I induction in astrocytes.
- To elucidate the mechanism by which MHV influences MHC class I expression.
Main Methods:
- In vitro culture of primary astrocytes.
- Infection with a panel of MHV strains.
- Measurement of MHC class I expression using radioimmunoassay.
- Assessment of viral infectivity and replication.
- Use of UV-inactivated viruses and recombinant viral strains.
Main Results:
- Hepatotropic MHV strains (e.g., MHV-A59) potently induced MHC class I expression in astrocytes, while neurotropic strains (e.g., JHMV) did not.
- MHC class I induction did not correlate with viral replication levels in astrocytes.
- Infectious virus, not a soluble factor, was required for MHC class I induction.
- Recombinant viral strain analysis indicated that a structural gene from MHV-A59 confers class I-inducing activity.
Conclusions:
- MHV strain-specific induction of MHC class I in astrocytes is a key feature of MHV infection.
- This induction is mediated by infectious virus and linked to specific viral structural genes.
- Findings contribute to understanding the immunopathogenesis of MHV-induced CNS disease and related human demyelinating conditions.