title: HIV-1 replication in human immune cells is independent of TAR DNA binding protein 43 (TDP-43) expression.
abstract: The TAR DNA binding protein (TDP-43) was originally identified as a host cell factor binding to the HIV-1 LTR and thereby suppressing HIV-1 transcription and gene expression (Ou et al., J.Virol. 1995, 69(6):3584). TDP-43 is a global regulator of transcription, can influence RNA metabolism in many different ways and is ubiquitously expressed. Thus, TDP-43 could be a major factor restricting HIV-1 replication at the level of LTR transcription and gene expression. These facts prompted us to revisit the role of TDP-43 for HIV-1 replication. We utilized established HIV-1 cell culture systems as well as primary cell models and performed a comprehensive analysis of TDP-43 function and investigated its putative impact on HIV-1 gene expression. In HIV-1 infected cells TDP-43 was neither degraded nor sequestered from the nucleus. Furthermore, TDP-43 overexpression as well as siRNA mediated knockdown did not affect HIV-1 gene expression and virus production in T cells and macrophages. In summary, our experiments argue against a restricting role of TDP-43 during HIV-1 replication in immune cells.
authors.affiliation: Institute of Virology, Helmholtz Zentrum Munich, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Nehls
authors.affiliation: Institute of Virology, Helmholtz Zentrum Munich, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Herwig
authors.initials: H
authors.lastname: Koppensteiner
authors.affiliation: Institute of Virology, Helmholtz Zentrum Munich, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Brack-Werner
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum Munich, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Floss
authors.affiliation: Institute of Virology, Helmholtz Zentrum Munich, German Research Center for Environmental Health, Neuherberg, Germany; Institute of Medical Virology and Epidemiology of Viral Diseases, University Clinic Tübingen, Tübingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schindler
mesh_terms: D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D057809:HEK293 Cells; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D021381:Protein Transport; D015533:Transcriptional Activation; D014779:Virus Replication
chemical_list: D004268:DNA-Binding Proteins; C000598624:TARDBP protein, human