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Targeting CCR5 trafficking to inhibit HIV-1 infection.

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.

SUBMITTER: Boncompain G

PROVIDER: S-EPMC6795511 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Targeting CCR5 trafficking to inhibit HIV-1 infection.

Boncompain Gaelle G Herit Floriane F Tessier Sarah S Lescure Aurianne A Del Nery Elaine E Gestraud Pierre P Staropoli Isabelle I Fukata Yuko Y Fukata Masaki M Brelot Anne A Niedergang Florence F Perez Franck F

Science advances 20191016 10

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 palmi ...[more]

PMID: 31663020

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