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

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 tr...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2015-12, Vol.486, p.94-104
Main Authors: Cobos Jiménez, Viviana, Martinez, Fernando O, Booiman, Thijs, van Dort, Karel A, van de Klundert, Maarten A.A, Gordon, Siamon, Geijtenbeek, Teunis B.H, Kootstra, Neeltje A
Format: Article
Language:English
Subjects:
Activated T-cells
Carrier Proteins - genetics
Carrier Proteins - metabolism
DNA Helicases
G3BP1
HIV Infections - enzymology
HIV Infections - genetics
HIV Infections - virology
HIV-1
HIV-1 - genetics
HIV-1 - physiology
Humans
IFNgamma
Infectious Disease
Macrophage activation
Macrophage transcriptome profiles
Macrophages - metabolism
Macrophages - virology
Poly-ADP-Ribose Binding Proteins
RNA Helicases
RNA Recognition Motif Proteins
RNA, Viral - genetics
RNA, Viral - metabolism
T-Lymphocytes - metabolism
T-Lymphocytes - virology
TNFalpha
Virus Replication
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Summary: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.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2015.09.007