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An In vitro Co-infection Model to Study Plasmodium falciparum-HIV-1 Interactions in Human Primary Monocyte-derived Immune Cells
Published on: August 15, 2012
Productive human immunodeficiency virus type 1 (HIV-1) infection of nonproliferating human monocytes
J B Weinberg1, T J Matthews, B R Cullen
1Department of Medicine, Veterans Affairs, Medical Center, Durham, North Carolina.
Insights
Human immunodeficiency virus type 1 (HIV-1) can infect monocytes, which are non-dividing cells, without requiring cellular proliferation or DNA synthesis. These infected monocytes may act as persistent reservoirs for HIV-1 in the body.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Human immunodeficiency virus type 1 (HIV-1) infection typically requires T lymphocyte proliferation and DNA synthesis.
- Human monocytes exhibit low DNA synthesis rates but can be efficiently infected by certain HIV-1 isolates.
Purpose of the Study:
- To investigate the mechanism of HIV-1 infection in non-proliferating human monocytes.
- To determine if cellular DNA synthesis is essential for HIV-1 replication in monocytes.
Main Methods:
- Infection of monocytes with the monocytotropic HIV-1 BaL isolate.
- Irradiation of monocytes to inhibit DNA synthesis.
- Analysis of HIV-1 DNA integration into chromosomal DNA.
Main Results:
- HIV-1 BaL efficiently infected monocytes, even when DNA synthesis was inhibited by irradiation.
- Infected monocytes showed integration of HIV-1 BaL DNA into their chromosomal DNA.
- Productive HIV-1 infection occurred in non-proliferating monocytes, unlike in T lymphocytes.
Conclusions:
- Normal, non-proliferating monocytes can be productively infected by HIV-1 independently of cellular DNA synthesis.
- Monocytes can serve as persistent and productive reservoirs for HIV-1 in vivo.
- Findings challenge the requirement of cellular proliferation for HIV-1 infection in certain cell types.
Abstract:
Human immunodeficiency virus type 1 (HIV-1) infection of T lymphocytes requires cellular proliferation and DNA synthesis. Human monocytes were shown to have low DNA synthesis rates, yet the monocytotropic BaL isolate of HIV-1 was able to infect these cells efficiently. Monocytes that were irradiated to assure no DNA synthesis could also be readily infected with HIV-1BaL. Such infections were associated with the integration of HIV-1BaL DNA into the high molecular weight, chromosomal DNA of monocytes. Thus, normal, nonproliferating monocytes differ from T lymphocytes in that a productive HIV-1 infection can occur independently of cellular DNA synthesis. These results suggest that normal nonproliferating mononuclear phagocytes, which are relatively resistant to the destructive effects of this virus, may serve as persistent and productive reservoirs for HIV-1 in vivo.
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