Abstract
More than 20 infectious agents, ranging from retroviruses to mycobacteria, have been associated with multiple sclerosis onset or relapses in which oligodendrocytes, the myelin-forming cells of the central nervous system, are the initial target of the pathogenic status. In this work, the nature of the susceptibility of the human precursor oligodendroglial KG-1C cell line to herpes simplex virus type 1 (HSV-1) was investigated. Infection of KG-1C cells was characterized by a high level of virus production and a notable progression of the cytopathic effect. After infection, there was a significant shut-off of host mRNA translation, which was correlated with evident synthesis of viral proteins. An examination by electron microscopy of the infected cells revealed the presence of large clusters of mitochondria located in the proximity of intracellular HSV-1 particle groups. In addition, transmission electron microscopy and nuclear fluorescence analysis showed neither signs of chromatin condensation nor of apoptotic bodies. Furthermore, procaspase-3 remained uncleaved, suggesting that apoptosis does not take place, at least in this system. Finally, expression and localization of MAL2, a subpopulation of detergent-insoluble lipid raft protein, was studied. Detection of MAL2 significantly increased after infection and it was colocalized with HSV-1 proteins. From these findings the authors conclude that human oligodendrocyte-like cells are highly susceptible to HSV-1 infection. The implications of this for central nervous system viral infection are discussed.
The authors are indebted to M.T. Rejas and M. Guerra for their help in the preparation and analysis of samples for electron microscopy, to C. Sánchez and R. Ramos for their help with fluorescence analysis, to Y. Uezono for the kind gift of the KG-1C cells, and to M.A. Alonso and M.C. de Marco for helpful discussions. This work was supported by grants PM99/0101 from the Ministerio de Ciencia y Tecnología and PI020920 from the Fondo de Investigación Sanitaria and the Junta de Andalucía. M. Fedetz is a fellow of the Fundación Carlos Haya.
