Journal
JOURNAL OF VIROLOGY
Volume 79, Issue 24, Pages 15405-15416Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.79.24.15405-15416.2005
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Funding
- NIAID NIH HHS [R01 AI045097, AI45097-6, R01 AI060686-01A1, R01 AI045097-07] Funding Source: Medline
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The effect of tumor necrosis factor alpha (TNF-alpha) on rabies virus (RV) infection of the mouse central nervous system (CNS) was studied, using recombinant RV engineered to express either soluble TNF-alpha [SPBN-TNF-alpha(+)] or insoluble membrane-bound TNF-alpha [SPBN-TNF-alpha(MEM)]. Growth curves derived from infections of mouse neuroblastoma NA cells revealed significantly less spread and production of SPBN-TNF-alpha(+) than of SPBN-TNF-alpha(MEM) or SPBN-TNF-alpha(-), which carries an inactivated TNF-alpha gene. The expression of soluble or membrane-bound TNF-alpha was not associated with increased cell death or induction of alpha/beta interferons. Brains of mice infected intranasally with SPBN-TNF-alpha(+) showed significantly less virus spread than did mouse brains after SPBN-TNF-alpha(-) infection, and none of the SPBN-TNF-alpha(+)infected mice succumbed to RV infection, whereas 80% of SPBN-TNF-alpha(-)-infected mice died. Reduced virus spread in SPBN-TNF-alpha(+)-infected mouse brains was paralleled by enhanced CNS inflammation, including T-cell infiltration and microglial activation. These data suggest that TNF-alpha 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.
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