The efficacy of potent anti-retroviral drug combinations tested in a murine model of HIV-1 encephalitis

J. Limoges; L. Poluektova; W. Ratanasuwan; J. Rasmussen; M. Zelivyanskaya; D. R. McClernon; E. R. Lanier; H. E. Gendelman; Y. Persidsky

doi:10.1006/viro.2000.0758

The efficacy of potent anti-retroviral drug combinations tested in a murine model of HIV-1 encephalitis

J. Limoges, L. Poluektova, W. Ratanasuwan, J. Rasmussen, M. Zelivyanskaya, D. R. McClernon, E. R. Lanier, H. E. Gendelman^*, Y. Persidsky

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Abstract

Development of anti-retroviral regimens with enhanced efficacy against brain HIV-1 is essential if viral eradication is to be achieved. To address this, a severe combined immune deficiency mouse model of HIV-1 encephalitis was used to assay the effect of protease-containing and protease-sparing drug regimens on viral replication in brain macrophages. Here, HIV-1-infected human monocyte-derived macrophages (MDM) are inoculated into basal ganglia, causing a multinucleated giant cell encephalitis reminiscent of human disease. Drugs were administered at the time of MDM inoculation and continued until sacrifice. Immunohistochemical tests evaluated ongoing viral replication, glial immunity, and neuronal survival. Treatment with ddl/d4T decreased the numbers of infected cells by 75%, while ddl/d4T/amprenavir or ZDV/3TC/ABC diminished infection by 98%. Triple drug regimens decreased astrogliosis by ≥25%. This small-animal model may be used to screen drug regimens that affect ongoing HIV-1 replication within its brain sanctuary.

Original language	English (US)
Pages (from-to)	21-34
Number of pages	14
Journal	Virology
Volume	281
Issue number	1
DOIs	https://doi.org/10.1006/viro.2000.0758
State	Published - Mar 1 2001

Keywords

HIV-1 encephalitis
Macrophages
Potent anti-retrovirals

ASJC Scopus subject areas

Virology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1006/viro.2000.0758

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title = "The efficacy of potent anti-retroviral drug combinations tested in a murine model of HIV-1 encephalitis",

abstract = "Development of anti-retroviral regimens with enhanced efficacy against brain HIV-1 is essential if viral eradication is to be achieved. To address this, a severe combined immune deficiency mouse model of HIV-1 encephalitis was used to assay the effect of protease-containing and protease-sparing drug regimens on viral replication in brain macrophages. Here, HIV-1-infected human monocyte-derived macrophages (MDM) are inoculated into basal ganglia, causing a multinucleated giant cell encephalitis reminiscent of human disease. Drugs were administered at the time of MDM inoculation and continued until sacrifice. Immunohistochemical tests evaluated ongoing viral replication, glial immunity, and neuronal survival. Treatment with ddl/d4T decreased the numbers of infected cells by 75%, while ddl/d4T/amprenavir or ZDV/3TC/ABC diminished infection by 98%. Triple drug regimens decreased astrogliosis by ≥25%. This small-animal model may be used to screen drug regimens that affect ongoing HIV-1 replication within its brain sanctuary.",

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note = "Funding Information: We thank Ms. Julie Ditter and Robin Taylor for excellent editorial support. Dr. Poluektova is a Nicolas Badami Research Fellow. This work was supported by National Institutes of Health Research Grants K08MH01552 (J.L.), R29AI42404 (Y.P.), and P01MH57556, P01NS31492, R01NS34239, and R01NS36126 (H.E.G.), and by GlaxoWellcome (Research Triangle Park, NC) (H.E.G.).",

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AU - Rasmussen, J.

AU - Zelivyanskaya, M.

AU - McClernon, D. R.

AU - Lanier, E. R.

AU - Gendelman, H. E.

AU - Persidsky, Y.

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N2 - Development of anti-retroviral regimens with enhanced efficacy against brain HIV-1 is essential if viral eradication is to be achieved. To address this, a severe combined immune deficiency mouse model of HIV-1 encephalitis was used to assay the effect of protease-containing and protease-sparing drug regimens on viral replication in brain macrophages. Here, HIV-1-infected human monocyte-derived macrophages (MDM) are inoculated into basal ganglia, causing a multinucleated giant cell encephalitis reminiscent of human disease. Drugs were administered at the time of MDM inoculation and continued until sacrifice. Immunohistochemical tests evaluated ongoing viral replication, glial immunity, and neuronal survival. Treatment with ddl/d4T decreased the numbers of infected cells by 75%, while ddl/d4T/amprenavir or ZDV/3TC/ABC diminished infection by 98%. Triple drug regimens decreased astrogliosis by ≥25%. This small-animal model may be used to screen drug regimens that affect ongoing HIV-1 replication within its brain sanctuary.

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The efficacy of potent anti-retroviral drug combinations tested in a murine model of HIV-1 encephalitis

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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