Differential Astrocyte Response to Theiler’s Murine Encephalomyelitis Virus Infection

Abstract

Objectives: We aimed to address if selective astrocyte apoptosis is involved in the lack of murine demyelinating disease following infection by the L*-1 variant of Theiler’s virus. In addition, we investigated whether L*-1-infected astrocytes were able to selectively express molecules whose effects would play a role as pathogenic factors. Methods: Murine cultured astrocytes were infected with two Theiler viruses, the DA strain and the mutated DA variant L*-1, which does not synthesize the out of frame L* protein. Results: Neither DA nor L*-1 provoked apoptosis, although they replicated in astrocytes inducing GFAP and iNOS expression, as well as subsequent nitric oxide production. In addition, both viruses caused an enhanced expression of ICAM-1, VCAM-1 and decay accelerating factor (DAF). In this connection, values of VCAM-1 and DAF induced by L*-1 were higher and lower, respectively, than those induced by DA. Conclusions: Since no apoptosis was found, such mechanism would not be involved in the lack of TMEV-induced demyelinating disease by L*-1. In contrast, selective expression of VCAM-1 and DAF molecules induced by L*-1 could have a role in virus clearance from the central nervous system.

Chronic restraint stress during early Theiler's virus infection exacerbates the subsequent demyelinating disease in SJL mice: II. CNS disease severity

“…Putative macrophages and activated astrocytes were found to be closely associated with areas of demyelination, a finding in agreement with previous research (Peña Rossi et al, 1997; Pozner et al, 2004; Rubio et al, 2006; Zheng et al, 2001). We also found that virus-positive cells were distributed centrally within newly forming lesions and in the periphery of more mature/developed lesions.…”

Brucella abortus Induces the Secretion of Proinflammatory Mediators from Glial Cells Leading to Astrocyte Apoptosis

“…[55][56][57][58] Also it has been reported for other microbial infections a cell-dependent susceptibility to apoptosis, 53,59 including a differential susceptibility of astrocytes and microglia. 60,61 TNF-␣ acts through two distinct cell surface receptors, TNFR1 and TNFR2. TNFR2 is expressed only on hematopoietic and endothelial cells, whereas TNFR1 is expressed on all cell types and initiates the majority of TNF-␣ biological activities.…”

The role of antigen presenting cells in multiple sclerosis

“…Inflammation induces astrocytes to produce cytokines that increase the blood brain barrier permeability, allowing easier infiltration by leukocytes [119]. In response to IFN-γ, TNF-α, and TMEV infection astrocytes upregulate ICAM-1 and VCAM-1 adhesion molecules which aids in leukocyte recruitment [123-125]. In response to IL-17, astrocytes produce CCL2, CCL12, CXCL1, and CXCL2, a distinctly different profile compared to IFN-γ stimulation [13, 60].…”