NFR1 plays a critical role in the control of severe HSV-1 encephalitis. TNFR1 plays a critical role in the control of severe HSV-1 encephalitis.

Herpes simplex virus-1 (HSV-1) is a pathogen for humans that may cause severe encephalitis. Tumor necrosis factor (TNF- ) plays a role in several viral diseases of the central nervous system (CNS). The classic proinflammatory activities of TNF- are mediated mainly through activation of the receptor 1 for TNF- (TNFR1). However, when HSV-1 is inoculated in the periphery, TNF- seems to protect C57Bl/6 mice against encephalitis by a mechanism independent of TNFR1. This study aims to investigate the role of TNFR1 in HSV-1 encephalitis induced by the inoculation of the virus into the brain. Wild-type C57BL/6 (WT) and TNFR1 ???/??? were inoculated with 102 plaque-forming units of HSV-1 by the intracranial route. Infection with HSV-1 was lethal in TNFR1 ???/??? mice in early times after infection. TNFR1???/??? mice had reduced expression of the chemokines CCL3 and CCL5, and decreased leukocyte adhesion in the brain vasculature compared to WT mice 4 days post-infection (dpi). At this time point TNFR1 ???/??? infected mice also had higher HSV-1 viral replication and more injuries in the brain, especially in the hippocampus. In conclusion, TNFR1 seems to play a relevant role in the control of viral replication in the CNS when HSV-1 is inoculated by intracranial route