AEGiS-12IAC: MIP-1 alpha, MIP-1 beta and RANTES beta-chemokines increase the replication of T-tropic HIV strains through CXCR4 stimulation.

12th International AIDS Conference

Geneva, Switzerland - June 28-July 3, 1998

MIP-1 alpha, MIP-1 beta and RANTES beta-chemokines increase the replication of T-tropic HIV strains through CXCR4 stimulation.

Int Conf AIDS 1998 Jun 28-Jul 3; 12:6 (abstract no. 11119)

Dolei A, Biolchini A, Serra C, Curreli S, Gomes E, Ziccmeddu M, Dianzi F, Dolei A
Dept. Biomedical Sciences, Univ. Sassari, Italy.

OBJECTIVE AND

DESIGN: It has been reported that beta-chemokines interfere in T lymphoid cells with the replication of monocytotropic (M-tropic) HIV-1 strains, but not with that of T-tropic strains, through their occupancy of the CCR5 receptor, used by M-tropic strains as co-receptor, and consequent perturbation of the process of HIV fusion with the plasmamembrane. Aim was to analyse the effects of MIP-1 alpha, MIP-1 beta and RANTES beta-chemokines on the replication in T cells of lymphocyte-tropic (T-tropic) HIV-1 strains.

METHODS: T lymphoid cells (freshly 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 graded amounts of beta-chemokines before infection with T-tropic HIV-1 isolates, or HTLV-IIIB. HIV replication was followed as production of infectious particles, p24 antigen and detection of viral DNA and RNA sequences. CXCR4 expression was followed by detection and quantification of specific transcripts.

RESULTS: Pretreatment of T cells with MIP-1 alpha, MIP-1 beta and RANTES can affect also T-tropic strains, as it increases dose-dependently the replication of HIV-1pi and HIV-1RPdT strains, as well as virus absorption and provirus DNA accumulation. These findings are associated to increased accumulation of CXCR4 transcripts, and mediated by the protein tyrosine kinase signalling. Moreover, beta-chemokines stimulate PBL proliferation.

CONCLUSIONS: At variance with published papers, our results show that beta-chemokines increase the adsorption and replication of at least some T-tropic HIV-1 strains, and this is related to stimulated expression of the CXCR4 co-receptor.

Keywords: AEGIS, Macrophage Inflammatory Protein-1, RANTES, Chemokines, CC, Virus Replication, Receptors, CCR5, HIV Infections, HIV-1, Receptors, CXCR4, Proviruses, T-Lymphocytes, Deltaretrovirus, HIV Seropositivity, DNA, Viral, Cell Line, Greece, virology, ICA12
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