Authors: | Rusconi, S.; Merill, D. P.; Catamancio, S. L.; Citterio, P.; Bulgheroni, E.; Croce, F.; Chou, T. C.; Yang, O. O.; Herrmann, S. H.; Galli, M.; Hirsch, M. S. |
Article Title: | In vitro inhibition of HIV-1 by Met-SDF-1beta alone or in combination with antiretroviral drugs |
Abstract: | Compounds that can block the CXCR4 chemokine receptor are a promising new class of antiretroviral agents. In these experiments we studied the effect of a modified form of the native stromal cell-derived factor-1 (SDF-1), Met-SDF-1 beta. The in vitro susceptibility of two different CXCR4-tropic HIV-1 strains was determined. Antiviral effect was assessed by the reduction of p24 antigen production in PHA-stimulated peripheral blood mononuclear cells with exposure to the modified SDF-1 molecule. The 50% inhibitory concentrations (IC50) were derived from six separate experiments. The IC50 against the two HIV-1 isolates was in 1.0-2.8 mug/ml range for Met-SDF-1 beta. Met-SDF-1 beta showed synergy to additivity with either zidovudine or nelfinavir at IC75, IC90 and IC95. Additivity was seen when Met-SDF-1 beta was combined with efavirenz. No cellular toxicity was observed at the highest concentrations when these agents were used either singly or in combination. This compound is a promising new candidate in a receptor-based approach to HIV-1 infection in conjunction with currently available combination antiretroviral drug therapies. |
Keywords: | infection; macrophages; immunodeficiency-virus type-1; recombinant; chemokine receptor cxcr4; small-molecule inhibitor; entry; soluble cd4; down-modulation; tropic hiv-1; coreceptor |
Journal Title: | Antiviral Therapy |
Volume: | 5 |
Issue: | 3 |
ISSN: | 1359-6535 |
Publisher: | International Medical Press |
Date Published: | 2000-01-01 |
Start Page: | 199 |
End Page: | 204 |
Language: | English |
ACCESSION: | WOS:000165097600004 |
PROVIDER: | wos |
PUBMED: | 11075940 |
Notes: | Article; Proceedings Paper -- 6th Conference on Retroviruses and Opportunistic Infections -- JAN 31-FEB 04, 1999 -- CHICAGO, ILLINOIS -- Source: Wos |