INCREASED REPLICATION OF T-CELL-TROPIC HIV STRAINS AND CXC-CHEMOKINE RECEPTOR-4 INDUCTION IN T-CELLS TREATED WITH MACROPHAGE INFLAMMATORY PROTEIN (MIP)-1-ALPHA, MIP-1-BETA AND RANTES BETA-CHEMOKINES

Objective and design: To study, in T-lymphoid cells, the effects of ma crophage inflammatory protein (MIP)-1 alpha, MIP-1 beta and RANTES bet a-chemokines on the replication of T-cell-tropic HIV-1 strains, since it has been reported that beta-chemokines interfere with the replicati on of macrophage-tropic HIV-1 strains, but not T-cell-tropic strains. Methods: Freshly phytohaemagglutinin (PHA)-activated peripheral blood lymphocytes (PBL) and cultured PHA-activated T cells from healthy volu nteers, as well as the C8166 T-cell line, were treated overnight with beta-chemokines before infection with T-cell-tropic HIV-1 isolates, or human T-lymphotropic virus type IIIB. HIV replication was followed by detecting the production of infectious particles, p24 antigen, and vi ral sequences. CXC-chemokine receptor (CXCR)-4 expression was followed by detection and quantification of specific transcripts. Results: Pre treatment of T cells with MIP-1 alpha, MIP-1 beta and RANTES affected T-cell-tropic strains, increased the replication of HIV-1(P1) and HIV- 1(RPdT) strains dose-dependently, as well as virus absorption and prov irus DNA accumulation. These findings were associated with increased a ccumulation of CXCR-4 transcripts, and mediated by the protein tyrosin e kinase signalling. Moreover, beta-chemokines stimulated PBL prolifer ation. Conclusions: beta-chemokines increase the adsorption and replic ation of at least some T-cell-tropic HIV-1 strains, and this is relate d to stimulated expression of the CXCR-4 coreceptor.