Aminooxypentane-RANTES, an inhibitor of R5 human immunodeficiency virus type 1, increases the interferon γ to interleukin 10 ratio without impairing cellular proliferation

Stefano Rusconi, Simona La Seta-Catamancio, Semir Kurtagic, Morena Galazzi, Donatella Arienti, Daria Trabattoni, Jill Wilken, Darren A. Thompson, Robin E. Offord, Massimo Galli, Mario Clerici

Research output: Contribution to journalArticlepeer-review

Abstract

Studies have demonstrated that the β-chemokines RANTES, MIP-1α, and MIP-1β suppress human immunodeficiency type 1 (HIV-1) replication in vitro. Infection with HIV-1 requires expression of CD4 antigen and the chemokine receptor CXCR4 (X4) or CCR5 (R5) on the surface of target cells. The engagement of these receptors with the viral surface proteins is essential for the membrane fusion process. This study investigated the anti-HIV-1 activity of a derivative of RANTES, the CCR5 antagonist aminooxypentane (AOP)-RANTES, on R5 HIV-1 isolates in peripheral blood mononuclear cells. In drug exposure experiments, AOP-RANTES efficiently inhibited viral replication of HIV-1 R5 strains, with a viral breakthrough observed after the withdrawal of the compound. The HIV-1-specific proliferative capacity was maintained under all conditions when compared with controls. An increase in IFN-γ production accompanied by a parallel decrease in the generation of IL-10 was observed following the in vitro exposure of cells to AOP-RANTES in the presence of three of four HIV-1 R5 isolates. These experiments confirmed that the chemokine receptor antagonist AOP-RANTES was effective as an inhibitor of HIV-1 R5 strain infectivity in peripheral blood mononuclear cells. The capacity of this compound to maintain HIV-1-specific proliferative activity with a shift toward a type 1 cytokine profile makes this compound a unique molecule, one adopting an immunological pathway to limit HIV-1 infection.

Original languageEnglish
Pages (from-to)861-867
Number of pages7
JournalAIDS Research and Human Retroviruses
Volume15
Issue number10
DOIs
Publication statusPublished - Jul 1 1999

ASJC Scopus subject areas

  • Immunology
  • Virology

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