Open AccessLack of both Fas Ligand and Perforin Protects from Flavivirus-Mediated Encephalitis in Mice
Author(s) -
Rosa María Licón Luna,
Eva Lee,
Arno Müllbacher,
Robert V. Blanden,
Rodney E. Langman,
Mario Lobigs
Publication year - 2002
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.76.7.3202-3211.2002
Subject(s) - biology , flavivirus , virology , encephalitis , virus , cytotoxic t cell , perforin , immunology , alphavirus , effector , immune system , cd8 , in vitro , biochemistry
The mechanism by which encephalitic flaviviruses enter the brain to inflict a life-threatening encephalomyelitis in a small percentage of infected individuals is obscure. We investigated this issue in a mouse model for flavivirus encephalitis in which the virus was administered to 6-week-old animals by the intravenous route, analogous to the portal of entry in natural infections, using a virus dose in the range experienced following the bite of an infectious mosquito. In this model, infection with 0.1 to 10(5) PFU of virus gave mortality in approximately 50% of animals despite low or undetectable virus growth in extraneural tissues. We show that the cytolytic effector functions play a crucial role in invasion of the encephalitic flavivirus into the brain. Mice deficient in either the granule exocytosis- or Fas-mediated pathway of cytotoxicity showed delayed and reduced mortality. Mice deficient in both cytotoxic effector functions were resistant to a low-dose peripheral infection with the neurotropic virus.