G3BP1 restricts HIV-1 replication in macrophages and T-cells by sequestering viral RNA

Viviana Cobos Jiménez, Fernando O. Martinez, Thijs Booiman, Karel A. van Dort, Maarten A. A. van de Klundert, Siamon Gordon, Teunis B. H. Geijtenbeek, Neeltje A. Kootstra

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22 Citations (Scopus)

Abstract

HIV-1 exploits the cellular machinery for replication and therefore several interactions with cellular factors take place, some of which are yet unknown. We identified GTPase-activating protein-(SH3 domain)-binding protein 1 (G3BP1) as a cellular factor that restricts HIV-1, by analyzing transcriptome profiles of in vitro-cytokine-activated macrophages that are non-permissive to HIV-1 replication. Silencing of G3BP1 by RNA interference resulted in increased HIV-1 replication in primary T-cells and macrophages, but did not affect replication of other retroviruses. G3BP1 specifically interacted with HIV-1 RNA in the cytoplasm, suggesting that it sequesters viral transcripts, thus preventing translation or packaging. G3BP1 was highly expressed in resting naïve or memory T-cells from healthy donors and HIV-1 infected patients, but significantly lower in IL-2-activated T-cells. These results strongly suggest that G3BP1 captures HIV-1 RNA transcripts and thereby restricts mRNA translation, viral protein production and virus particle formation
Original languageEnglish
Pages (from-to)94-104
JournalVirology
Volume486
DOIs
Publication statusPublished - 2015

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