Increased replication of T-cell-tropic HIV strains and CXC-chemokine receptor-4 induction in T cells treated with macrophage inflammatory protein (MIP)-1α, MIP-1β and RANTES β-chemokines


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Abstract

Objective and design:To study, in T-lymphoid cells, the effects of macrophage inflammatory protein (MIP)-1α, MIP-1β and RANTES β-chemokines on the replication of T-cell-tropic HIV-1 strains, since it has been reported that β-chemokines interfere with the replication 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 volunteers, as well as the C8166 T-cell line, were treated overnight with β-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 viral sequences. CXC-chemokine receptor (CXCR)-4 expression was followed by detection and quantification of specific transcripts.Results:Pretreatment of T cells with MIP-1α, MIP-1β and RANTES affected T-cell-tropic strains, increased the replication of HIV-1P1 and HIV-1RPdT strains dose-dependently, as well as virus absorption and provirus DNA accumulation. These findings were associated with increased accumulation of CXCR-4 transcripts, and mediated by the protein tyrosine kinase signalling. Moreover, β-chemokines stimulated PBL proliferation.Conclusions:β-Chemokines increase the adsorption and replication of at least some T-cell-tropic HIV-1 strains, and this is related to stimulated expression of the CXCR-4 coreceptor.

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