Extracellular HIV-1 tat protein up-regulates the expression of surface CXC-chemokine receptor 4 in resting CD4+ T cells.
Here we report that synthetic HIV-1 Tat protein, immobilized on a solid substrate, up-regulates the surface expression of the CXC-chemokine receptor 4 (CXCR4), but not of the CC-chemokine receptor 5 in purified populations of primary resting CD4+ T cells. The Tat-mediated increase of CXCR4 occurred in a well-defined range of concentrations (1-10 nM of immobilized Tat) and time period (4-8 h postincubation). Moreover, the increase of CXCR4 was accompanied by an increased entry of the HXB2 T cell line-tropic (X4-tropic), but not of the BaL macrophage-tropic strain of HIV-1. The ability of Tat to up-regulate CXCR4 expression was abrogated by the protein synthesis inhibitor cycloheximide, clearly indicating the requirement of de novo synthesis. As Tat protein is actively released by HIV-1 infected cells, our data indicate a potentially important role for extracellular Tat in rendering bystander CD4+ T cells more susceptible to infection with X4-tropic HIV-1 isolates.
Secchiero
P
P
Institute of Human Virology, University of Maryland Biotechnology Institute, Baltimore 21201, USA. secchier@umbi.umd.edu
Zella
D
D
Capitani
S
S
Gallo
R C
RC
Zauli
G
G
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D005110:Extracellular Space / Q000276:immunology / Q000821:virology*; D015696:Gene Products, tat / Q000138:chemical synthesis / Q000494:pharmacology / Q000502:physiology*; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D007399:Interphase / Q000187:drug effects / Q000276:immunology*; D014176:Protein Biosynthesis; D019718:Receptors, CXCR4 / Q000096:biosynthesis*; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology*; D054322:tat Gene Products, Human Immunodeficiency Virus