Cofactors for human immunodeficiency virus entry into primary macrophages.
Macrophages are permissive for macrophage-tropic (M-tropic) human immunodeficiency virus type 1 (HIV-1) isolates that use CCR5 for entry but are resistant to CXCR-4-dependent T cell-tropic prototype strains. M-tropic variants are critical for HIV-1 transmission, and persons who are homozygous for an inactivating mutation of CCR5 are resistant to HIV-1 in vivo. In vitro, their macrophages and lymphocytes are resistant to M-tropic strains that depend on CCR5. It is shown that CCR5-deficient macrophages are permissive for a dual-tropic isolate, 89.6, that uses CCR5, CXCR-4, and other cofactors. Entry by 89.6 into CCR5-deficient macrophages was blocked by the CXCR-4 ligand SDF and by an anti-CXCR-4 antibody. Immunoflorescence staining and reverse transcription PCR confirmed macrophage CXCR-4 expression. Thus, CXCR-4 on macrophages mediates entry of certain dual-tropic but not T cell-tropic isolates. Therefore, HIV-1 strains differ in how they utilize chemokine receptors as cofactors for entry, and the ability of a chemokine receptor to facilitate entry depends on the cell in which it is expressed.
Collman
R G
RG
Pulmonary and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6060, USA. collmanr@mail. med.upenn.edu
Yi
Y
Y
D005434:Flow Cytometry; D015497:HIV-1 / Q000145:classification / Q000472:pathogenicity*; D006801:Humans; D007113:Immunity, Innate; D066298:In Vitro Techniques; D008264:Macrophages / Q000821:virology*; D016133:Polymerase Chain Reaction; D054390:Receptors, CCR2; D054397:Receptors, CCR3; D019713:Receptors, CCR5 / Q000378:metabolism*; D054401:Receptors, CCR8; D019718:Receptors, CXCR4 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism; D015728:Receptors, HIV / Q000378:metabolism
C515334:CCR2 protein, human; C515350:CCR3 protein, human; C103330:CCR8 protein, human; D054390:Receptors, CCR2; D054397:Receptors, CCR3; D019713:Receptors, CCR5; D054401:Receptors, CCR8; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D015728:Receptors, HIV