Related Experiment Videos
The restricted nature of HIV-1 tropism for cultured neural cells
N Sharpless1, D Gilbert, B Vandercam
1Laboratory of Viral and Molecular Pathogenesis, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892.
Abstract:
Infection of the central nervous system by HIV-1, the agent of AIDS, is characterized by the presence of infected and giant microglial cells as well as astrocytosis, demyelination, and neuronal loss. To determine whether cells of neuroectoderm origin can be infected by HIV-1, we have inoculated primary cultures derived from adult human brain with a lymphotropic virus (LAV) or a neurotropic virus (Jr-FL) isolated from a patient with AIDS dementia. While Jr-FL invariably causes productive infection of cultured brain microglia, neither astrocytes nor oligodendrocytes became productively infected by these viral strains. Moreover, the cultured oligodendrocytes develop a normal network of processes and express differentiation antigens in the presence of an ongoing lytic infection of microglial cells. No HIV-1 proviral DNA was detected in primary astrocyte cultures devoid of microglial after inoculation of either HIV-1 strain. Similarly, the neuronal cell line HCN-1 in its differentiated state did not allow the virus to go through cycles of reverse transcription and replication. LAV, however, was able to replicate in undifferentiated HCN-1 cells. Thus, tropism of HIV-1 appears tightly restricted to only one type of differentiated cell in the CNS, the microglia.
Insights
Human Immunodeficiency Virus-1 (HIV-1) primarily infects microglia in the central nervous system. Other brain cells like astrocytes and oligodendrocytes are resistant to productive HIV-1 infection, indicating specific viral tropism.
Area of Science:
- Neuroscience
- Virology
- Immunology
Background:
- Human Immunodeficiency Virus-1 (HIV-1) infection of the central nervous system (CNS) leads to neurological damage.
- Key neuropathological features include microglial activation, astrocytosis, demyelination, and neuronal loss.
Purpose of the Study:
- To investigate the susceptibility of various human brain cells to HIV-1 infection.
- To determine the tropism of HIV-1 within the CNS.
Main Methods:
- Primary cultures of adult human brain cells (microglia, astrocytes, oligodendrocytes) were inoculated with lymphotropic (LAV) and neurotropic (Jr-FL) HIV-1 strains.
- Neuronal cell line (HCN-1) was used in both differentiated and undifferentiated states.
- Viral replication and proviral DNA presence were assessed.
Main Results:
- The neurotropic Jr-FL strain productively infected cultured microglia.
- Astrocytes and oligodendrocytes showed no productive infection by either viral strain.
- Differentiated HCN-1 cells resisted viral replication, while undifferentiated cells supported LAV replication.
- No HIV-1 proviral DNA was detected in microglial-free astrocyte cultures.
Conclusions:
- HIV-1 tropism in the CNS is restricted to microglia.
- Differentiated neurons are generally resistant to HIV-1 infection, though some viral replication may occur in undifferentiated neuronal states.