Actin-Dependent Receptor Colocalization Required for Human Immunodeficiency Virus Entry into Host Cells |
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| Authors: | Sujatha Iyengar James E K Hildreth and David H Schwartz |
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| Institution: | Department of Pharmacology and Molecular Sciences, School of Medicine,1. and Department of Molecular Microbiology and Immunology, School of Hygiene and Public Health,2. The Johns Hopkins University, Baltimore, Maryland 21205 |
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| Abstract: | Human immunodeficiency virus (HIV) envelope binds CD4 and a chemokine receptor in sequence, releasing hydrophobic viral gp41 residues into the target membrane. HIV entry required actin-dependent concentration of coreceptors, which could be disrupted by cytochalasin D (CytoD) without an effect on cell viability or mitosis. Pretreatment of peripheral blood mononuclear cells, but not virus, inhibited entry and infection. Immunofluorescent confocal microscopy of activated cells revealed CD4 and CXCR4 in nonoverlapping patterns. Addition of gp120 caused polarized cocapping of both molecules with subsequent pseudopod formation, while CytoD pretreatment blocked these membrane changes completely. |
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