As part of the Scripps AIDS Dementia Center grant, we have established a feline colony for the purpose of developing the FIV/Cat system as an animal model to study the neurologic aspects of AIDS. Because of the success in developing this model, the number of investigators and experiments utilizing this system has precipitously grown since the Center's inception. Thus, the requirement for cats from both within and outside of the Center has exceeded the available funds to support the research. In this proposal, we request assistance to help further develop the FIV/Cat system as an animal model for the neurologic aspects of HIV-1 induced disease. This colony serves our Center's researchers as well as several collaborating investigators. Thus, our colony can be considered of emerging national importance. We have made great strides in developing the feline/FIV model as a legitimate system for the study of lentivirus induced neurologic disease, as several parameters have been established to monitor the effects of virus infection on the CNS. However, to fully develop the FIV/Cat system, further studies are required. Developing the FIV/Cat system as a predictive animal model to examine the effects of treatment interventions on the neurologic aspects of the disease would enhance the utility of this modeling system. To this end, we now want to expand our ongoing studies to investigate the effects of antivirals on neurologic aspects of the disease as well as the adaptive response of the virus to the drug. We propose the following specific aims: 1) Specifically develop the FIV/cat system as an animal model for examining effects of antivirals on the neurologic disease progression of lentivirus infections. 2) Monitor the animals for the development of drug-resistant mutants and map the genetic determinants associated with the resistant phenotype. 3) determine if FIV-drug resistant mutants maintain their neurovirulence. Our long term objective is to develop the FIV-cat system as a predictive animal model for assessing the effects of antiviral compounds on the neurologic aspects of lentivirus diseases. The completion of these specific aims will further validate the FIV/cat system as a predictive animal model as well as provide valuable insights into virus-host-drug interactions, thus, further establishing and refining the FIV/cat system as a research resource.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Resource-Related Research Projects (R24)
Project #
5R24RR010712-08
Application #
6446868
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Robinson, Jerry
Project Start
1995-04-01
Project End
2003-08-31
Budget Start
2001-09-01
Budget End
2002-08-31
Support Year
8
Fiscal Year
2001
Total Cost
$375,358
Indirect Cost
Name
Vaccine Research Institute of San Diego
Department
Type
DUNS #
City
San Diego
State
CA
Country
United States
Zip Code
92109
Huitron-Resendiz, Salvador; Henriksen, Steven J; Barr, Margaret C et al. (2010) Methamphetamine and lentivirus interactions: reciprocal enhancement of central nervous system disease. J Neurovirol 16:268-78
Cloak, C C; Chang, L; Ernst, T et al. (2004) Methamphetamine and AIDS: 1HMRS studies in a feline model of human disease. J Neuroimmunol 147:16-20
Barr, Margaret C; Huitron-Resendiz, Salvador; Sanchez-Alavez, Manuel et al. (2003) Escalating morphine exposures followed by withdrawal in feline immunodeficiency virus-infected cats: a model for HIV infection in chronic opiate abusers. Drug Alcohol Depend 72:141-9
Hart, Richard A; Billaud, Jean-Noel; Choi, Sam J et al. (2002) Effects of 1,8-diaminooctane on the FIV Rev regulatory system. Virology 304:97-104
Sharma, Sanjay K; Billaud, Jean-Noel; Tandon, Manju et al. (2002) Inhibition of feline immunodeficiency virus (FIV) replication by DNA binding polyamides. Bioorg Med Chem Lett 12:2007-10
Billet, O; Billaud, J N; Phillips, T R (2001) Partial characterization and tissue distribution of the feline mu opiate receptor. Drug Alcohol Depend 62:125-9
Billaud, J N; Ly, C; Phillips, T R et al. (2000) Borna disease virus persistence causes inhibition of glutamate uptake by feline primary cortical astrocytes. J Virol 74:10438-46
Phillips, T R; Billaud, J N; Henriksen, S J (2000) Methamphetamine and HIV-1: potential interactions and the use of the FIV/cat model. J Psychopharmacol 14:244-50
Billaud, J N; Selway, D; Yu, N et al. (2000) Replication rate of feline immunodeficiency virus in astrocytes is envelope dependent: implications for glutamate uptake. Virology 266:180-8
Barr, M C; Huitron-Resendiz, S; Selway, D R et al. (2000) Exogenous glucocorticoids alter parameters of early feline immunodeficiency virus infection. J Infect Dis 181:576-86

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