Specific tropism of HIV-1 for microglial cells in primary human brain cultures

Article Abstract:

Human immunodeficiency virus (HIV, the virus responsible for AIDS) infects several types of cells in the body, including T lymphocytes (white blood cells), monocyte-macrophage cells (white blood cells active in engulfing and destroying foreign particles), and cells in the central nervous system (CNS). Infection of the CNS leads to neurological impairment and can ultimately be associated with the loss of cognitive function known as AIDS dementia. Infection of the CNS by HIV-1 (HIV, type 1) has been seen in several brain regions, and in several cell types. It appears that the main sites of viral replication in the CNS are cells that belong to the macrophage-monocyte system. Microglial cells are a type of cells within this system that normally perform immune functions, and their infection by HIV-1 could have important consequences for the brain's defense against AIDS. To learn more about the effects of HIV infection on microglial cells, human brain cells were grown in tissue culture and infected with several strains of HIV-1 and HIV-2. When infection had been accomplished, the cells were examined to see which types expressed the viral antigen (indicating that viral replication took place). Changes in several variables associated with microglia were noted in the presence of infection with certain strains of HIV-1, such as clustering, fusion, and death. Astrocytes, another type of brain glial cell, did not express viral antigen or show pathologic change. Some of the patterns observed in cell culture were similar to those identified in the brains of AIDS patients with neurological changes. Overall, microglia appear particularly susceptible to infection by this virus and well able to support HIV replication. A discussion is provided of the possible effects of microglial infection in AIDS, which include impaired immune functioning and possible destruction of nerve cells by release of toxic factors as they die. (Consumer Summary produced by Reliance Medical Information, Inc.)

Infection, Complications and side effects, Brain, Macrophages

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Quiescent T lymphocytes as an inducible virus reservoir in HIV-1 infection

Article Abstract:

The human immunodeficiency virus type 1 (HIV-1) is located primarily in T lymphocytes that contain the CD4 protein. Studies have shown that ten to one hundred times more T lymphocytes contain virus that is not actively replicating, compared with cells where the virus is replicating. This suggests that in the majority of cells, HIV-1 is in a latent state that can be induced or activated to replicate. The state of HIV in the cells (if activated or latent) was examined in patients in various stages of HIV infection. In 11 patients who were infected with the virus but did not have any symptoms of disease (asymptomatic), the majority of the virus was found in the latent state. The virus was present in the cells, but was not inserted into the genes in the cell, a step necessary for the virus to replicate or be active. This form of the virus could integrate into the genes of the cells if the cells were stimulated, as occurs in an immune response to infection. In seven patients with AIDS, increased levels of the inserted form of the virus were present. Even in these patients, unstimulated T cells contained virus that was not inserted into the genes of the cells. Therefore, these T cells could act as a reservoir for the virus, which could become activated if the cells were stimulated; this could occur in various aspects of the disease, such as the development of opportunistic infections. (Consumer Summary produced by Reliance Medical Information, Inc.)

CD4 lymphocytes

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Retroviral DNA integration directed by HIV integration protein in vitro

Article Abstract:

The replication of retroviruses, including the human immunodeficiency virus (HIV), requires the integration, or insertion, of viral DNA (deoxyribonucleic acid) into the DNA of the host. A system was devised to allow integration to be studied in vitro (outside of the body, for example in a test tube), without any cells. The system requires the HIV integration (IN) protein. The IN protein was obtained from cells that were genetically engineered to produce large amounts of the protein. Integration was measured by the insertion of DNA containing viral sequences into additional DNA. This study shows that the HIV IN protein is the only viral protein that is necessary for the integration of viral DNA into the host DNA. Additional cellular and viral proteins were shown to increase the levels of integration. In this cell-free system, the properties of the IN protein can be studied. This system can be used to test various drugs which might be effective against HIV infections by inhibiting the viral IN protein and viral integration. (Consumer Summary produced by Reliance Medical Information, Inc.)

Retroviruses

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