当前位置： SCI文献检索 > JOURNAL OF NEUROIMMUNOLOGY期刊下所有文献 > Astrocytes, not microglia, are the main cells responsible for viral persistence in Theiler's murine encephalomyelitis virus infection leading to demyelination.

Astrocytes, not microglia, are the main cells responsible for viral persistence in Theiler's murine encephalomyelitis virus infection leading to demyelination.

Abstract：

:The BeAn strain of Theiler's murine encephalomyelitis virus (TMEV) persists in the CNS and produces a chronic inflammatory demyelinating disease that is an animal model for human multiple sclerosis (MS). The mechanisms leading to TMEV-induced demyelination are still under study but most likely involve both immune-mediated and virus induced damage to cells in the CNS, both depending on viral persistence. It is therefore important to identify the cells in which continued virus production is permitted. In this study, we looked at virus infection in primary astrocytes, microglia and oligodendrocytes, derived from brains of neonatal susceptible SJL/J mice. As evidenced by Western blots and immunocytochemistry, we were able to detect viral antigens in all these brain-derived cells. In addition, we extended the study to spinal cord tissues from mice suffering TMEV-induced disease. Immunohistochemistry staining with anti-TMEV sera and antibodies to specific cell markers detected viral antigens in all these cells. We then asked the question whether viral antigen present in these cells, particularly in microglia/macrophages, represented true viral replication or not. By using different techniques, including immunoprecipitation experiments and the very sensitive method of negative RNA detection through RNase protection assay, we show that both astrocytes and oligodendroglia permit de novo viral replication and viral protein synthesis but with only minimal cytopathic effects. Of these two cell types, astrocytes carry the brunt of viral replication. In microglia, on the other hand, viral replication is restricted since only minimal amounts of negative RNA copies can be demonstrated, while there are clear signs that some of these cells undergo apoptosis. These findings show that the main cell for viral replication is the astrocyte, rather than the microglia/macrophage. Most of the viral antigen present in macrophages, therefore, is probably the result of phagocytosis, rather than actual viral replication. In view of the demonstrated presence of viral replication in astrocytes and of great amounts of viral antigens in microglia/macrophages, it is possible that both types of cells act as antigen presenting cells during this immunopathological disease.

journal_name

J Neuroimmunol

journal_title

Journal of neuroimmunology

authors

Zheng L,Calenoff MA,Dal Canto MC

doi

10.1016/s0165-5728(01)00338-1

subject

Has Abstract

pub_date

2001-08-30 00:00:00

pages

256-67

issue

eissn

0165-5728

issn

1872-8421

pii

S0165572801003381

journal_volume

118

pub_type

杂志文章

在线工具

Astrocytes, not microglia, are the main cells responsible for viral persistence in Theiler's murine encephalomyelitis virus infection leading to demyelination.