CXCR4 as a Functional Coreceptor for Human Immunodeficiency Virus Type 1 Infection of Primary Macrophages

Author:

Simmons Graham1,Reeves Jacqueline D.1,McKnight Áine1,Dejucq Nathalie1,Hibbitts Sam1,Power Christine A.2,Aarons Emma3,Schols Dominique4,De Clercq Erik4,Proudfoot Amanda E. I.2,Clapham Paul R.1

Affiliation:

1. Section of Virology, Chester Beatty Laboratories, Institute of Cancer Research, London SW3 6JB,1 and

2. Serono Pharmaceutical Research Institute, 1228 Plan-les-Ouates, Geneva, Switzerland2; and

3. Department of Genito-urinary Medicine, Jefferiss Research Trust Laboratories, Imperial College School of Medicine at St. Mary’s, London WL 1NY,3 United Kingdom;

4. Rega Institute for Medical Research, Katholiche Universiteit Leuven, B-3000 Leuven, Belgium4

Abstract

ABSTRACT The coreceptors used by primary syncytium-inducing (SI) human immunodeficiency virus type 1 isolates for infection of primary macrophages were investigated. SI strains using only CXCR4 replicated equally well in macrophages with or without CCR5 and were inhibited by several different ligands for CXCR4 including SDF-1 and bicyclam derivative AMD3100. SI strains that used a broad range of coreceptors including CCR3, CCR5, CCR8, CXCR4, and BONZO infected CCR5-deficient macrophages about 10-fold less efficiently than CCR5 + macrophages. Moreover, AMD3100 blocked infection of CCR5-negative macrophages by these strains. Our results therefore demonstrate that CXCR4, as well as CCR5, is used for infection of primary macrophages but provide no evidence for the use of alternative coreceptors.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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