TY - JOUR
T1 - G3BP1 restricts HIV-1 replication in macrophages and T-cells by sequestering viral RNA
AU - Cobos Jiménez, Viviana
AU - Martinez, Fernando O.
AU - Booiman, Thijs
AU - van Dort, Karel A.
AU - van de Klundert, Maarten A.A.
AU - Gordon, Siamon
AU - Geijtenbeek, Teunis B.H.
AU - Kootstra, Neeltje A.
N1 - Publisher Copyright:
© 2015 Published by Elsevier Inc.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - 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.
AB - 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.
KW - Activated T-cells
KW - G3BP1
KW - HIV-1
KW - IFNgamma
KW - Macrophage activation
KW - Macrophage transcriptome profiles
KW - TNFalpha
UR - https://www.scopus.com/pages/publications/84942808161
U2 - 10.1016/j.virol.2015.09.007
DO - 10.1016/j.virol.2015.09.007
M3 - 文章
C2 - 26432022
AN - SCOPUS:84942808161
SN - 0042-6822
VL - 486
SP - 94
EP - 104
JO - Virology
JF - Virology
ER -
