Targeting CCR5 Trafficking to Inhibit HIV-1 Infection

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2019 Oct 31

PMID 31663020

Citations 13

Authors

Gaelle Boncompain

Floriane Herit

Sarah Tessier

Aurianne Lescure

Elaine Del Nery

Pierre Gestraud

Isabelle Staropoli

Yuko Fukata

Masaki Fukata

Anne Brelot

Florence Niedergang

Franck Perez

Affiliations

Soon will be listed here.

Abstract

Using a cell-based assay monitoring differential protein transport in the secretory pathway coupled to high-content screening, we have identified three molecules that specifically reduce the delivery of the major co-receptor for HIV-1, CCR5, to the plasma membrane. They have no effect on the closely related receptors CCR1 and CXCR4. These molecules are also potent in primary macrophages as they markedly decrease HIV entry. At the molecular level, two of these molecules inhibit the critical palmitoylation of CCR5 and thereby block CCR5 in the early secretory pathway. Our results open a clear therapeutics avenue based on trafficking control and demonstrate that preventing HIV infection can be performed at the level of its receptor delivery.

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