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Microglia in human disease, with an emphasis on acquired immune deficiency syndrome
D W Dickson1, L A Mattiace, K Kure
1Department of Pathology, Neuropathology, Albert Einstein College of Medicine, Bronx, NY 10461.
Abstract:
In conclusion, there is overwhelming evidence that within the CNS the primary sites of active HIV-1 infection are microglia. CNS infection may be related to the normal repopulation of the CNS by monocytes (microglial turnover) that carry latent infection into the CNS. Activation of viral infection may depend upon microglial differentiation, soluble factors (cytokines), and/or coexistent infections. Infection of microglia may disturb the normal hemostatic balance that exists between microglia and other glia, and between microglia and neurons, processes that are only recently being explored at the molecular level. The impact that HIV infection of microglia may have on synaptic integrity is unknown. Cytokines appear to be prime candidates as mediators of some of the adverse effects of microglial infection on other CNS cells, myelin and endothelial cells.
Insights
Microglia are the main sites of active Human Immunodeficiency Virus type 1 (HIV-1) infection in the central nervous system (CNS). This infection may disrupt CNS homeostasis and impact neuronal and glial cells, potentially mediated by cytokines.
Area of Science:
- Neuroscience
- Immunology
- Virology
Background:
- The central nervous system (CNS) is a primary target for Human Immunodeficiency Virus type 1 (HIV-1) infection.
- Microglia, the resident immune cells of the CNS, are increasingly recognized as key players in HIV-1 neuropathogenesis.
Purpose of the Study:
- To elucidate the primary sites of active HIV-1 infection within the CNS.
- To explore the mechanisms of HIV-1 entry and activation within microglia.
- To understand the consequences of microglial HIV-1 infection on CNS homeostasis and cellular function.
Main Methods:
- The study synthesizes existing evidence on HIV-1 infection within the CNS.
- It examines the role of monocyte infiltration and microglial turnover in viral dissemination.
- It discusses the influence of microglial differentiation, cytokines, and co-infections on viral activation.
Main Results:
- Overwhelming evidence indicates microglia are the primary sites of active HIV-1 infection in the CNS.
- HIV-1 may enter the CNS via monocytes, which differentiate into microglia.
- Microglial infection can disrupt the balance between microglia, other glia, and neurons.
Conclusions:
- Microglial infection by HIV-1 is a critical factor in CNS pathogenesis.
- Cytokines are implicated as mediators of adverse effects on CNS cells, myelin, and endothelial cells.
- The impact on synaptic integrity remains an area for future research.