Neurology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Correspondence:
Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when Correspondence are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Limoges, J.
Right arrow Articles by Gendelman, H. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Limoges, J.
Right arrow Articles by Gendelman, H. E.
Neurology 2000;54:379
© 2000 American Academy of Neurology
Articles

Evaluation of antiretroviral drug efficacy for HIV-1 encephalitis in SCID mice

J. Limoges, MD, Y. Persidsky, MD, PhD, L. Poluektova, MD, PhD, J. Rasmussen, BS, W. Ratanasuwan, MD, M. Zelivyanskaya, DVM, D. R. McClernon, BS, E. R. Lanier, PhD and H. E. Gendelman, MD

From the Center for Neurovirology and Neurodegenerative Disorders and the Departments of Pathology and Microbiology (Drs. Persidsky, Poluektova, Ratanasuwan, Zelivyanskaya, and Gendelman, and J. Rasmussen) and Internal Medicine (Drs. Limoges and Gendelman), University of Nebraska Medical Center, Omaha, NE; and Glaxo Wellcome, Inc. (Dr. Lanier and D.R. McClernon), Research Triangle Park, NC.

Address correspondence and reprint requests to Dr. Y. Persidsky, Center for Neurovirology and Neurodegenerative Disorders, 985215 Nebraska Medical Center, Omaha, NE 68198-5215; e-mail: ypersids{at}mail.unmc.edu

OBJECTIVES: To compare the efficacy of the nucleoside reverse transcriptase inhibitors (NRTIs) abacavir, zidovudine (AZT), lamivudine (3TC), didanosine (ddI), and stavudine (d4T) to inhibit viral replication in brain macrophages. A severe combined immunodeficiency (SCID) mouse model of HIV-1 encephalitis (HIVE) was used to monitor spreading viral infection in the CNS. Background: The development of antiretroviral therapies with CNS efficacy against neuroinvasive virus is important if eradication of HIV-1 can be achieved within critical "hidden reservoirs."

METHODS: HIV-1–infected human monocyte–derived macrophages (MDMs) (after a single round of viral replication) were inoculated into the caudate and putamen of SCID mice. This resulted in the spreading of viral infection with a concomitant multinucleated giant cell encephalitis (astrogliosis, microglial activation, and neuronal injury). NRTIs were administered to animals at the time of intracerebral MDM inoculations and continued until the time of sacrifice. Antiretroviral effects were assessed by viral load and percentages of infected MDMs.

RESULTS: In brains of SCID mice with HIVE, abacavir and lamivudine reduced HIV-1 p24 antigen–positive cells by 80% and 95%, respectively, whereas both decreased viral load by ~1 log. Zidovudine, didanosine, and stavudine showed variable effects.

CONCLUSIONS: Abacavir and lamivudine showed significant antiretroviral activity in SCID mice with HIVE when compared with other NRTIs. The extrapolation of these results to humans with HIV-1 dementia awaits future investigations.

Key words: HIV-1 encephalitis—HIV-1–associated dementia—Antiretrovirals—Animal model




This article has been cited by other articles:


Home page
 J. Leukoc. Biol.Home page
S. Aquaro, V. Svicher, D. Schols, M. Pollicita, A. Antinori, J. Balzarini, and C. F. Perno
Mechanisms underlying activity of antiretroviral drugs in HIV-1-infected macrophages: new therapeutic strategies
J. Leukoc. Biol., November 1, 2006; 80(5): 1103 - 1110.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
Y. Persidsky and H. E. Gendelman
Mononuclear phagocyte immunity and the neuropathogenesis of HIV-1 infection
J. Leukoc. Biol., November 1, 2003; 74(5): 691 - 701.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
H. Dou, K. Birusingh, J. Faraci, S. Gorantla, L. Y. Poluektova, S. B. Maggirwar, S. Dewhurst, H. A. Gelbard, and H. E. Gendelman
Neuroprotective Activities of Sodium Valproate in a Murine Model of Human Immunodeficiency Virus-1 Encephalitis
J. Neurosci., October 8, 2003; 23(27): 9162 - 9170.
[Abstract] [Full Text] [PDF]

Home page
 CVIHome page
C. E. Nesbit and S. A. Schwartz
In Vitro and Animal Models of Human Immunodeficiency Virus Infection of the Central Nervous System
Clin. Vaccine Immunol., May 1, 2002; 9(3): 515 - 524.
[Full Text] [PDF]

Home page
 J. Immunol.Home page
L. Y. Poluektova, D. H. Munn, Y. Persidsky, and H. E. Gendelman
Generation of Cytotoxic T Cells Against Virus-Infected Human Brain Macrophages in a Murine Model of HIV-1 Encephalitis
J. Immunol., April 15, 2002; 168(8): 3941 - 3949.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
S. A. Thomas, A. Bye, and M. B. Segal
Transport Characteristics of the Anti-human Immunodeficiency Virus Nucleoside Analog, Abacavir, into Brain and Cerebrospinal Fluid
J. Pharmacol. Exp. Ther., September 1, 2001; 298(3): 947 - 953.
[Abstract] [Full Text]

Home page
 NeurologyHome page
J. C. McArthur and K. Kieburtz
Of mice and men: A model of HIV encephalitis
Neurology, January 25, 2000; 54(2): 284 - 284.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2000 by AAN Enterprises, Inc.