Oligodendroglial degeneration in distemper: apoptosis or necrosis?

Canine distemper virus (CDV) causes a multifocal demyelinating disease in d ogs. It was previously shown that the initial demyelinating lesions are dir ectly virus induced since a correlation between the occurrence of demyelina tion and CDV replication in white matter cells was observed. During the cou rse of infection oligodendrocytes undergo distinct morphological alteration s, partly due to a restricted CDV infection of these cells, and eventually disappear from the lesions. This phenomenon has been described in vivo as w ell as in vitro. However, the reason for the morphological alterations and the following oligodendroglial depletion remained unclear. Since virus infe ction can induce cell death, it was investigated whether apoptosis or necro sis plays a role in the pathogenesis of demyelination in canine distemper. In brain tissue sections from dogs with acute distemper apoptotic cells wer e not detected within the demyelinating lesions using morphological and bio chemical cell death criteria. In chronic distemper, apoptotic cells - presu mably inflammatory cells - were seen within the perivascular cuffs. These i n vivo findings were correlated to the in vitro situation using CDV-infecte d primary dog brain cell cultures as well as Vero cells. Infection with cul ture-adapted CDV lead to massive necrosis but not to apoptosis. After infec tion with virulent CDV neither apoptosis nor necrosis was a predominant fea ture in either culture system. These findings suggest that virus-induced de myelination in canine distemper is not the direct consequence of apoptosis or necrosis. It is speculated that another mechanism must be responsible fo r the observed morphological alterations of oligodendrocytes, ultimately le ading to demyelination.