| Abstract |
Infection of susceptible mice with Theiler's murine encephalomyelitis
virus (TMEV) represents an important animal model to study the
pathogenesis of multiple sclerosis (MS). Similar to MS, the TMEV-induced
demyelinating disease is initiated by immune-mediated processes;
remyelination is rarely observed and usually incomplete. Moreover,
proliferating oligodendrocyte precursor cells (OPCs) are increased in
number in and outside the demyelinating plaques. OPCs are of particular
relevance because they are the potential source of new myelin-forming
oligodendrocytes in adult mammals. So far, it is not known, whether OPCs
are targeted by TMEV, and if yes, how they respond to the infection. In
the present study, a novel OPC cell line, termed BO-1, was created from
SJL/J TMEV-susceptible mice by spontaneous immortalization. The aims of
the study were (1) to characterize the antigenic phenotype and the
differentiation capacity of BO-1 cells in vitro, (2) to investigate
whether TMEV in vitro targets BO-1 cells displaying a specific antigenic
phenotype, and (3) to determine the effects of TMEV infection on the
differentiation capacity of BO-1 cells in vitro. BO-1 cells maintained in
B104-conditioned medium displayed a bi-to multipolar morphology and
expressed several typical antigenic markers for primary OPCs in vitro.
Although BO-1 cells did not respond to thyroid hormone treatment,
differentiation towards oligodendrocytes and type-2 astrocytes was
promoted by retinoic acid and fetal calf serum, respectively. Moreover, co-
culturing of BO-1 cells with primary astrocytes further increased the
expression of oligodendrocytic markers, supporting the idea that the
immortalized BO-1 cells retained several characteristics of primary OPCs.
TMEV in vitro preferentially infected BO-1 cells expressing early OPC
markers, such as A2B5 and NG2. Moreover, TMEV infection inhibited
differentiation of BO-1 cells into oligodendrocytes. This observation may
help to explain the limited remyelination observed in TMEV-IDD in vivo.
Further studies focusing on the cellular and molecular aspects of TMEV
infection of BO-1 cells are needed to gain a better understanding of virus
mediated alterations of cellular differentiation.
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