title: Resolution and prevention of feline immunodeficiency virus-induced neurological deficits by treatment with the protease inhibitor TL-3.
abstract: In vivo tests were performed to assess the influence of the protease inhibitor TL-3 on feline immunodeficiency virus (FIV)-induced central nervous system (CNS) deficits. Twenty cats were divided into four groups of five animals each. Group 1 received no treatment, group 2 received TL-3 only, group 3 received FIV strain PPR (FIV-PPR) only, and group 4 received FIV-PPR and TL-3. Animals were monitored for immunological and virological status, along with measurements of brain stem auditory evoked potential (BAEP) changes. Groups 1 and 2 remained FIV negative, and groups 3 and 4 became virus positive and seroconverted by 3 to 5 weeks postinoculation. No adverse effects were noted with TL-3 only. The average peak viral load for the virus-only group 3 animals was 1.32 x 10(6) RNA copies/ml, compared to 6.9 x 10(4) copies/ml for TL-3-treated group 4 cats. Group 3 (virus-only) cats exhibited marked progressive delays in BAEPs starting at 2 weeks post virus exposure, which is typical of infection with FIV-PPR. In contrast, TL-3-treated cats of group 4 exhibited BAEPs similar to those of control and drug-only cats. At 97 days postinfection, treatments were switched; i.e., group 4 animals were taken off TL-3 and group 3 animals were treated with TL-3. BAEPs in group 3 animals returned to control levels, while BAEPs in group 4 animals remained at control levels. After 70 days on TL-3, group 3 was removed from the drug treatment regimen. Delays in BAEPs immediately increased to levels observed prior to TL-3 treatment. The findings show that early TL-3 treatment can effectively eliminate FIV-induced changes in the CNS. Furthermore, TL-3 can counteract FIV effects on the CNS of infected cats, although continued treatment is required to maintain unimpaired CNS function.
authors.affiliation: Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Salvador
authors.initials: S
authors.lastname: Huitron-Resendiz
authors.forename: Sohela
authors.initials: S
authors.lastname: De Rozières
authors.forename: Manuel
authors.initials: M
authors.lastname: Sanchez-Alavez
authors.forename: Bernd
authors.initials: B
authors.lastname: Bühler
authors.forename: Ying-Chuan
authors.initials: YC
authors.lastname: Lin
authors.forename: Danica L
authors.initials: DL
authors.lastname: Lerner
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Henriksen
authors.forename: Mboya
authors.initials: M
authors.lastname: Burudi
authors.forename: Howard S
authors.initials: HS
authors.lastname: Fox
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Torbett
authors.forename: Steven
authors.initials: S
authors.lastname: Henriksen
authors.forename: John H
authors.initials: JH
authors.lastname: Elder
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000187:drug effects; D002371:Cat Diseases / Q000188:drug therapy / Q000503:physiopathology / Q000821:virology; D002415:Cats; D002493:Central Nervous System Diseases / Q000188:drug therapy* / Q000517:prevention & control* / Q000821:virology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D016181:Feline Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000503:physiopathology / Q000821:virology; D016089:Immunodeficiency Virus, Feline / Q000187:drug effects* / Q000472:pathogenicity; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D011480:Protease Inhibitors