title: 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 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.
authors.affiliation: Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, and Center for Infectious Diseases and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Amsterdam 1105AZ, The Netherlands.
authors.forename: Viviana
authors.initials: V
authors.lastname: Cobos Jiménez
authors.affiliation: Kennedy Rheumatology Institute, University of Oxford, Oxford OX3 7LD, United Kingdom.
authors.forename: Fernando O
authors.initials: FO
authors.lastname: Martinez
authors.affiliation: Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, and Center for Infectious Diseases and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Amsterdam 1105AZ, The Netherlands.
authors.forename: Thijs
authors.initials: T
authors.lastname: Booiman
authors.affiliation: Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, and Center for Infectious Diseases and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Amsterdam 1105AZ, The Netherlands.
authors.forename: Karel A
authors.initials: KA
authors.lastname: van Dort
authors.affiliation: Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, and Center for Infectious Diseases and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Amsterdam 1105AZ, The Netherlands.
authors.forename: Maarten A A
authors.initials: MA
authors.lastname: van de Klundert
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
authors.forename: Siamon
authors.initials: S
authors.lastname: Gordon
authors.affiliation: Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, and Center for Infectious Diseases and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Amsterdam 1105AZ, The Netherlands.
authors.forename: Teunis B H
authors.initials: TB
authors.lastname: Geijtenbeek
authors.affiliation: Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, and Center for Infectious Diseases and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Amsterdam 1105AZ, The Netherlands. Electronic address: N.A.Kootstra@amc.uva.nl.
authors.forename: Neeltje A
authors.initials: NA
authors.lastname: Kootstra
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004265:DNA Helicases; D015658:HIV Infections / Q000201:enzymology* / Q000235:genetics / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000378:metabolism* / Q000821:virology; D000075223:Poly-ADP-Ribose Binding Proteins; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism* / Q000821:virology; D014779:Virus Replication
chemical_list: D002352:Carrier Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D000067776:RNA Recognition Motif Proteins; D012367:RNA, Viral; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases
keywords: Activated T-cells; G3BP1; HIV-1; IFNgamma; Macrophage activation; Macrophage transcriptome profiles; TNFalpha