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Journal of Virology, May 2004, p. 4525-4532, Vol. 78, No. 9
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.9.4525-4532.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Resolution and Prevention of Feline Immunodeficiency Virus-Induced Neurological Deficits by Treatment with the Protease Inhibitor TL-3

Salvador Huitron-Resendiz,1,{dagger} Sohela de Rozières,2,{dagger} Manuel Sanchez-Alavez,1 Bernd Bühler,3 Ying-Chuan Lin,2 Danica L. Lerner,2 Nicholas W. Henriksen,1 Mboya Burudi,1 Howard S. Fox,1 Bruce E. Torbett,3 Steven Henriksen,1 and John H. Elder2*

Department of Neuropharmacology,1 Department of Molecular Biology,2 Department of Experimental Medicine, The Scripps Research Institute, La Jolla, California3

Received 13 November 2003/ Accepted 22 December 2003

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 106 RNA copies/ml, compared to 6.9 x 104 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.

* Corresponding author. Mailing address: The Scripps Research Institute, Department of Molecular Biology, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 784-8270. Fax: (858) 784-2750. E-mail: jelder{at}scripps.edu.

{dagger} Salvador Huitron-Resendiz and Sohela de Rozières contributed equally to this study.

Journal of Virology, May 2004, p. 4525-4532, Vol. 78, No. 9
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.9.4525-4532.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • de Rozieres, S., Thompson, J., Sundstrom, M., Gruber, J., Stump, D. S., de Parseval, A. P., VandeWoude, S., Elder, J. H. (2008). Replication Properties of Clade A/C Chimeric Feline Immunodeficiency Viruses and Evaluation of Infection Kinetics in the Domestic Cat. J. Virol. 82: 7953-7963 [Abstract] [Full Text]  


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