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 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.
Vilela
Márcia Carvalho
MC
Departamento de Clínica Médica, Faculdade de Medicina (FM), UFMG, Belo Horizonte, Brazil. marciacvilela@gmail.com
Lima
Graciela Kunrath
GK
Rodrigues
David Henrique
DH
Lacerda-Queiroz
Norinne
N
Mansur
Daniel Santos
DS
de Miranda
Aline Silva
AS
Rachid
Milene Alvarenga
MA
Kroon
Erna Geessien
EG
Vieira
Leda Quercia
LQ
Campos
Marco Antônio
MA
Teixeira
Mauro Martins
MM
Teixeira
Antônio Lúcio
AL
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
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