Inhibition of coreceptor-independent cell-to-cell human immunodeficiency virus type 1 transmission by a CD4-immunoglobulin G2 fusion protein

Berta Bosch, Julià Blanco, Eduardo Pauls, Imma Clotet-Codina, Mercedes Armand-Ugón, Boyan Grigorov, Delphine Muriaux, Bonaventura Clotet, Jean Luc Darlix, José A. Esté

Research output: Contribution to journalArticleResearchpeer-review

20 Citations (Scopus)

Abstract

We have previously shown (J. Blanco et al., J. Biol. Chem. 279:51305-51314, 2004) that the contact between HIV producing cells and primary CD4+ T cells may induce the uptake of human immunodeficiency virus (HIV) particles by target cells in the absence of HIV envelope-mediated membrane fusion or productive HIV replication. HIV uptake by CD4+ T cells was dependent on cellular contacts mediated by the binding of gp120 to CD4 but was independent of the expression of the appropriate HIV coreceptor, CCR5 or CXCR4. Here, we have characterized the effect of agents blocking gp120 binding to CD4 on cell-to-cell HIV transmission. A recombinant CD4-based protein (CD4-immunoglobulin G2 [IgG2]), that is currently being evaluated in clinical trials, completely inhibited the uptake of HIV particles by CD4+ T cells from persistently infected cells expressing R5, X4, or X4/T-20-resistant HIV-1 envelope glycoproteins. Consequently, both the release of viral particles from endocytic vesicles and the infection of reporter U87-CD4 cells were also prevented. The polyanionic anti-HIV agent dextran sulfate failed to prevent the intracellular uptake of virions by CD4+ T cells. Indeed, it increased HIV uptake in a dose-dependent manner, suggesting functional differences between the specific gp120-targeting CD4-IgG2 agent and nonspecific HIV binding inhibitors. Thus, the inhibition of the specific interaction between gp120 and CD4 protein could be an effective strategy to inhibit HIV binding to CD4 + T cells, and the mechanism by which CD4+ T cells lacking the appropriate coreceptor may be converted in HIV carriers. Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Original languageEnglish
Pages (from-to)4296-4304
JournalAntimicrobial Agents and Chemotherapy
Volume49
Issue number10
DOIs
Publication statusPublished - 1 Oct 2005

Fingerprint Dive into the research topics of 'Inhibition of coreceptor-independent cell-to-cell human immunodeficiency virus type 1 transmission by a CD4-immunoglobulin G2 fusion protein'. Together they form a unique fingerprint.

Cite this