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Cofactors for human immunodeficiency virus entry into primary macrophages
1Pulmonary and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6060, USA. collmanr@mail. med.upenn.edu
The Journal of Infectious Diseases
|April 1, 1999
Summary
Macrophages allow entry of macrophage-tropic (M-tropic) HIV-1 strains. However, CXCR-4 on macrophages enables entry of certain dual-tropic HIV-1 strains, not T-cell tropic ones.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Macrophages are permissive to macrophage-tropic (M-tropic) HIV-1 strains utilizing CCR5.
- T-cell tropic strains dependent on CXCR-4 cannot infect macrophages.
- CCR5 mutations confer resistance to M-tropic HIV-1 in vivo and in vitro.
Purpose of the Study:
- To investigate the role of CXCR-4 in HIV-1 entry into macrophages.
- To determine if macrophages express functional CXCR-4 for viral entry.
Main Methods:
- Utilized CCR5-deficient macrophages.
- Tested entry of dual-tropic HIV-1 isolate 89.6.
- Employed SDF-1 ligand and anti-CXCR-4 antibody for blocking experiments.
- Confirmed CXCR-4 expression using immunofluorescence and RT-PCR.
Main Results:
- CCR5-deficient macrophages were permissive to dual-tropic isolate 89.6.
- Entry of 89.6 into these macrophages was blocked by CXCR-4 targeting agents.
- Macrophage CXCR-4 expression was confirmed.
Conclusions:
- CXCR-4 on macrophages mediates entry of specific dual-tropic HIV-1 strains.
- HIV-1 strains exhibit differential utilization of chemokine receptors for entry.
- Chemokine receptor function in viral entry is cell-type dependent.