In vitro modeling of the HIV-macrophage reservoir
Amanda Brown1, Hao Zhang, Peter Lopez
1Johns Hopkins School of Medicine, Department of Neurology, 600 North Wolfe St., Baltimore, MD 21287, USA. abrown76@jhmi.edu
Journal of Leukocyte Biology
|August 23, 2006
Summary
Human macrophages can harbor latent HIV-1 infection. This study developed a model to show that infected macrophages can maintain integrated HIV provirus, with a subset capable of reactivation, suggesting a viral reservoir.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Macrophages are suspected HIV-1 reservoirs.
- The capacity for latent HIV infection in macrophages remains unconfirmed.
Purpose of the Study:
- To investigate if HIV can establish a latent infection in primary human monocyte-derived macrophages (MDM).
- To characterize the replication dynamics of HIV in long-term macrophage cultures.
Main Methods:
- Developed an in vitro model using EGFP-tagged HIV in cultured MDM.
- Utilized flow cytometry and laser ablation for cell purification.
- Employed Alu-LTR real-time PCR to detect integrated provirus.
Main Results:
- Identified a subpopulation of infected MDM (GFP hi) with high early gene transcription but low late gene (p24) production.
- Purified GFP- MDM populations contained integrated HIV provirus.
- A subset of these latent cells were replication-competent upon IL-4 reactivation.
Conclusions:
- HIV can establish a latent infection in human macrophages.
- Infected macrophages exhibit alternative replication modes, potentially contributing to viral persistence.
- This macrophage model provides insights into HIV latency and reservoir dynamics.
