title: TNFR1 plays a critical role in the control of severe HSV-1 encephalitis.
abstract: Herpes simplex virus-1 (HSV-1) is a pathogen for humans that may cause severe encephalitis. Tumor necrosis factor alpha (TNF-alpha) plays a role in several viral diseases of the central nervous system (CNS). The classic proinflammatory activities of TNF-alpha are mediated mainly through activation of the receptor 1 for TNF-alpha (TNFR1). However, when HSV-1 is inoculated in the periphery, TNF-alpha 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 10(2) 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.
authors.affiliation: Departamento de Clínica Médica, Faculdade de Medicina (FM), UFMG, Belo Horizonte, Brazil. marciacvilela@gmail.com
authors.forename: Márcia Carvalho
authors.initials: MC
authors.lastname: Vilela
authors.forename: Graciela Kunrath
authors.initials: GK
authors.lastname: Lima
authors.forename: David Henrique
authors.initials: DH
authors.lastname: Rodrigues
authors.forename: Norinne
authors.initials: N
authors.lastname: Lacerda-Queiroz
authors.forename: Daniel Santos
authors.initials: DS
authors.lastname: Mansur
authors.forename: Aline Silva
authors.initials: AS
authors.lastname: de Miranda
authors.forename: Milene Alvarenga
authors.initials: MA
authors.lastname: Rachid
authors.forename: Erna Geessien
authors.initials: EG
authors.lastname: Kroon
authors.forename: Leda Quercia
authors.initials: LQ
authors.lastname: Vieira
authors.forename: Marco Antônio
authors.initials: MA
authors.lastname: Campos
authors.forename: Mauro Martins
authors.initials: MM
authors.lastname: Teixeira
authors.forename: Antônio Lúcio
authors.initials: AL
authors.lastname: Teixeira
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D054405:Chemokine CCL3 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D020803:Encephalitis, Herpes Simplex / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D018259:Herpesvirus 1, Human; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism*; D012720:Severity of Illness Index; D016019:Survival Analysis
chemical_list: C496534:Ccl3 protein, mouse; C503460:Ccl5 protein, mouse; D054405:Chemokine CCL3; D018946:Chemokine CCL5; D047888:Receptors, Tumor Necrosis Factor, Type I; C506236:Tnfrsf1a protein, mouse