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Actin-dependent receptor colocalization required for human immunodeficiency virus entry into host cells
S Iyengar1, J E Hildreth, D H Schwartz
1Department of Pharmacology and Molecular Sciences, School of Medicine, The Johns Hopkins University, Baltimore, Maryland 21205, USA.
Journal of Virology
|May 30, 1998
Summary
Human immunodeficiency virus (HIV) entry into cells depends on coreceptor concentration, which is actin-dependent. Disrupting this process with cytochalasin D (CytoD) blocks viral entry and infection without harming cells.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- Human immunodeficiency virus (HIV) envelope proteins mediate viral entry by binding to CD4 and chemokine receptors.
- This sequential binding facilitates the release of viral gp41, inserting into the target cell membrane.
Purpose of the Study:
- To investigate the role of actin-dependent coreceptor clustering in HIV entry.
- To determine the effect of cytochalasin D (CytoD) on HIV coreceptor dynamics and viral infection.
Main Methods:
- Utilized immunofluorescent confocal microscopy to visualize CD4 and CXCR4 distribution on activated peripheral blood mononuclear cells (PBMCs).
- Assessed the impact of cytochalasin D (CytoD) on coreceptor clustering, pseudopod formation, and HIV entry and infection.
- Investigated the effect of CytoD pretreatment on PBMCs versus the virus itself.
Main Results:
- HIV entry was found to be dependent on the actin-dependent concentration of coreceptors (CD4 and CXCR4).
- CytoD disrupted this coreceptor clustering and subsequent pseudopod formation, completely blocking viral membrane changes.
- Pretreatment of PBMCs, but not the virus, with CytoD inhibited HIV entry and infection, without affecting cell viability or mitosis.
Conclusions:
- Actin-dependent clustering of CD4 and chemokine receptors is essential for efficient HIV entry.
- Targeting the actin cytoskeleton or coreceptor dynamics presents a potential strategy for inhibiting HIV infection.