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Identification of EcoHIV-Infected Cells in Microglia-Manipulated Transgenic Mice
Published on: December 20, 2024
HIV-1 replication in the central nervous system occurs in two distinct cell types
Gretja Schnell1, Sarah Joseph, Serena Spudich
1Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, North Carolina, United States of America.
Plos Pathogens
|October 19, 2011
Summary
Human immunodeficiency virus type 1 (HIV-1) central nervous system (CNS) infection can cause dementia. Two distinct HIV-1 viral strains in cerebrospinal fluid (CSF) were identified in dementia patients, suggesting different replication patterns and origins in the CNS.
Area of Science:
- Neurovirology
- Immunology
- Genetics
Background:
- Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) is linked to HIV-1-associated dementia (HAD).
- Understanding viral characteristics in the CNS is crucial for elucidating dementia development.
Purpose of the Study:
- To investigate the virological features of HIV-1 within the cerebrospinal fluid (CSF) of individuals with HAD.
- To explore the relationship between distinct viral replication in the CNS and the manifestation of dementia.
Main Methods:
- Analysis of HIV-1 genetic diversity and tropism in CSF samples from HAD patients.
- Correlation of viral characteristics with clinical data, including response to therapy and CD4+ T-cell counts.
Main Results:
- Two independent HIV-1 populations were identified in CSF: CCR5-tropic (R5) T cell-tropic and macrophage-tropic viruses.
- Macrophage-tropic viruses showed genetic diversity, indicating established CNS infection, while R5 T cell-tropic viruses were clonally amplified and linked to pleocytosis.
- R5 viruses required high CD4+ levels for entry and showed rapid decay with therapy, unlike macrophage-tropic viruses, which entered cells with low CD4+ and exhibited slow decay, suggesting a long-lived cellular reservoir.
Conclusions:
- Distinct virological states within the CNS contribute to HAD.
- Macrophage-tropic viruses are largely confined to the CNS and can persist in long-lived cells.
- CSF viral analysis offers insights into CNS viral replication and evolution, crucial for understanding HIV-associated neurocognitive disorders.
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