Actin-Dependent Receptor Colocalization Required for Human Immunodeficiency Virus Entry into Host Cells

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J Virol, June 1998, p. 5251-5255, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Actin-Dependent Receptor Colocalization Required for Human Immunodeficiency Virus Entry into Host Cells

Sujatha Iyengar,¹ James E. K. Hildreth,¹ and David H. Schwartz²^,^*

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

Received 23 October 1997/Accepted 3 March 1998

Human immunodeficiency virus (HIV) envelope binds CD4 and a chemokine receptor in sequence, releasing hydrophobic viral gp41residues into the target membrane. HIV entry required actin-dependentconcentration of coreceptors, which could be disrupted by cytochalasinD (CytoD) without an effect on cell viability or mitosis. Pretreatmentof peripheral blood mononuclear cells, but not virus, inhibitedentry and infection. Immunofluorescent confocal microscopy ofactivated cells revealed CD4 and CXCR4 in nonoverlapping patterns.Addition of gp120 caused polarized cocapping of both moleculeswith subsequent pseudopod formation, while CytoD pretreatmentblocked these membrane changes completely.

^* Corresponding author. Mailing address: Department of Molecular Microbiology and Immunology, Johns Hopkins School of Hygieneand Public Health, 615 N. Wolfe St., Baltimore, MD 21205. Phone:(410) 955-3175. Fax: (410) 955-0105. E-mail: dschwart{at}jhsph.edu.

J Virol, June 1998, p. 5251-5255, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

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