SEX-DIFFERENCES IN SUSCEPTIBILITY TO VIRAL-INFECTION OF THE CENTRAL-NERVOUS-SYSTEM

We have characterized striking differences in recovery of male and fem ale BALB/c and BALB/c-H-2(dm2) (dm2) mice from an experimental neurotr opic viral infection of the central nervous system (CNS). Following in tranasal inoculation of vesicular stomatitis virus (VSV), assays of ti ssue homogenates from female mice produced lower viral titers. There w as also a significant reduction in the spread of virus from the rostra l to caudal end of the brain in female mice. Enhanced recovery by fema le mice of both strains in response to this viral insult correlates wi th increased levels of Nitric Oxide Synthase (NOS) types I, II, and II I expression, an increased prevalence of reactive astrocytes, earlier and enhanced levels of expression of Major Histocompatabilty Complex ( MHC) class II molecules on astrocytes, endothelial and microglial cell s, and increased T cell infiltration in the female BALB/c mouse. Taken together, these findings document sexual dimorphism in CNS immunity, and may provide an understanding of some of the mechanisms underlying many sex-biased diseases.