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-1β. 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 μg/ml range for Met-SDF-1β. Met-SDF-1β showed synergy to additivity with either zidovudine or nelfinavir at IC75, IC90 and IC95. Additivity was seen when Met-SDF-1β 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.

In vitro inhibition of HIV-1 by Met-SDF-1β alone or in combination with antiretroviral drugs / S. Rusconi, D.P. Merrill, S. La Seta Catamancio, P. Citterio, E. Bulgheroni, F. Croce, T.-. Chou, O.O. Yang, S.H. Herrmann, M. Galli, M.S. Hirsch. - In: ANTIVIRAL THERAPY. - ISSN 1359-6535. - 5:3(2000), pp. 199-204. ((Intervento presentato al 6. convegno Conference on Retroviruses and Opportunistic Infections tenutosi a Chicago nel 1999.

In vitro inhibition of HIV-1 by Met-SDF-1β alone or in combination with antiretroviral drugs

S. Rusconi;S. La Seta Catamancio;P. Citterio;E. Bulgheroni;F. Croce;M. Galli;
2000

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-1β. 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 μg/ml range for Met-SDF-1β. Met-SDF-1β showed synergy to additivity with either zidovudine or nelfinavir at IC75, IC90 and IC95. Additivity was seen when Met-SDF-1β 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.
Settore MED/17 - Malattie Infettive
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/754981
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