title: TRIM19/PML Restricts HIV Infection in a Cell Type-Dependent Manner.
abstract: The promyelocytic leukemia protein (PML) is the main structural component of the nuclear matrix structures termed nuclear domain 10 (ND10) or PML nuclear bodies (PML-NBs). PML and ND10 structures have been shown to mediate an intrinsic immune response against a variety of different viruses. Their role during retroviral replication, however, is still controversially discussed. In this study, we analyzed the role of PML and the ND10 components Daxx and Sp100 during retroviral replication in different cell types. Using cell lines exhibiting a shRNA-mediated knockdown, we found that PML, but not Daxx or Sp100, inhibits HIV and other retroviruses in a cell type-dependent manner. The PML-mediated block to retroviral infection was active in primary human fibroblasts and murine embryonic fibroblasts but absent from T cells and myeloid cell lines. Quantitative PCR analysis of HIV cDNA in infected cells revealed that PML restricts infection at the level of reverse transcription. Our findings shed light on the controversial role of PML during retroviral infection and show that PML contributes to the intrinsic restriction of retroviral infections in a cell type-dependent manner.
authors.affiliation: Institute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany. tanja_sanchez@yahoo.com.
authors.forename: Tanja
authors.initials: T
authors.lastname: Kahle
authors.affiliation: Institute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany. bavolkma@viro.med.uni-erlangen.de.
authors.forename: Bianca
authors.initials: B
authors.lastname: Volkmann
authors.affiliation: Institute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany. kristin.eissmann@viro.med.uni-erlangen.de.
authors.forename: Kristin
authors.initials: K
authors.lastname: Eissmann
authors.affiliation: Institute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany. alexandra.herrmann@viro.med.uni-erlangen.de.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Herrmann
authors.affiliation: Institute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany. sven.schmitt3@gmx.de.|Institute of Clinical Chemistry and Pharmacology, University Hospital Bonn, 53127 Bonn, Germany. sven.schmitt3@gmx.de.
authors.forename: Sven
authors.initials: S
authors.lastname: Schmitt
authors.affiliation: Institute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany. sabine.wittmann@viro.med.uni-erlangen.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Wittmann
authors.affiliation: Institute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany. lamerkel@viro.med.uni.erlangen.de.
authors.forename: Laura
authors.initials: L
authors.lastname: Merkel
authors.affiliation: Institute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany. nina.reuter@viro.med.uni-erlangen.de.
authors.forename: Nina
authors.initials: N
authors.lastname: Reuter
authors.affiliation: Institute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany. tsstammi@viro.med.uni-erlangen.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Stamminger
authors.affiliation: Institute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany. thomas.gramberg@fau.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gramberg
mesh_terms: D000818:Animals; D005347:Fibroblasts / Q000276:immunology / Q000821:virology; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology*; D000071156:Promyelocytic Leukemia Protein; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D009687:Nuclear Proteins; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human
keywords: HIV-1; ND10; PML; TRIM19; intrinsic immunity; retrovirus