Abstract
Cytomegalovirus (CMV) is the leading transmittable cause of congenital brain abnormalities in children and infection results in fatal ventriculoencephalitis in advanced acquired immunodeficiency syndrome (AIDS) patients. Pathology associated with CMV brain infection is seen predominantly in the periventricular region, an area known to harbor neural stem cells (NSCs). In the present study, using an adult model of murine CMV brain infection, the authors demonstrated that nestin-positive NSCs in the subventricular zone are susceptible to murine CMV infection. Furthermore, primary NSC cultures supported productive murine CMV replication with a 1000-fold increase in viral titers by 5 days post infection (d.p.i). Previous studies from the authors’ laboratory demonstrated that CD8 lymphocytes were essential in protecting the brain against murine CMV infection. In the present study, the authors found that interferon (IFN)-γ treatment increased the expression of major histocompatibility complex (MHC) class I on NSCs. Viral infection, on the other hand, inhibited this IFN-γ–induced MHC up-regulation. In addition to increasing MHC class I expression, IFN-γ (but not tumor necrosis factor [TNF]-α, interleukin [IL]-1β, or IL-10) also suppressed NSC proliferation in vitro. This decrease in proliferation was not accompanied by apoptosis or extracellular release of cellular lactate dehydrogenase (LDH), suggesting that the effects were not due to direct cytotoxicity. These studies demonstrate that NSCs are susceptible to murine CMV infection and inflammatory mediators, such as IFN-γ, alter cellular characteristics which may have an impact on their reparative functions.
Acknowledgements
This work was supported by United States Public Health Service grant NS-038836. The authors thank Thomas Bakken for skillful technical assistance in the conduct of these studies. The authors would also like to thank Drs. Genya Gekker and Manohar Mutnal for their technical input. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.