ABSTRACT
The effect of tumor necrosis factor alpha (TNF-α) on rabies virus (RV) infection of the mouse central nervous system (CNS) was studied, using recombinant RV engineered to express either soluble TNF-α [SPBN-TNF-α(+)] or insoluble membrane-bound TNF-α [SPBN-TNF-α(MEM)]. Growth curves derived from infections of mouse neuroblastoma NA cells revealed significantly less spread and production of SPBN-TNF-α(+) than of SPBN-TNF-α(MEM) or SPBN-TNF-α(−), which carries an inactivated TNF-α gene. The expression of soluble or membrane-bound TNF-α was not associated with increased cell death or induction of alpha/beta interferons. Brains of mice infected intranasally with SPBN-TNF-α(+) showed significantly less virus spread than did mouse brains after SPBN-TNF-α(−) infection, and none of the SPBN-TNF-α(+)-infected mice succumbed to RV infection, whereas 80% of SPBN-TNF-α(−)-infected mice died. Reduced virus spread in SPBN-TNF-α(+)-infected mouse brains was paralleled by enhanced CNS inflammation, including T-cell infiltration and microglial activation. These data suggest that TNF-α exerts its protective activity in the brain directly through an as yet unknown antiviral mechanism and indirectly through the induction of inflammatory processes in the CNS.
α‐Tocopherol, but Not γ‐Tocopherol, Attenuates the Expression of Selective Tumor Necrosis Factor‐Alpha‐Induced Genes in Primary Human Aortic Cell Lines