PuSH - Publikationsserver des Helmholtz Zentrums München: HIV-1 replication in human immune cells is independent of TAR DNA binding Protein 43 (TDP-43) expression.

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Nehls, J. ; Koppensteiner, H. ; Brack-Werner, R. ; Floß, T. ; Schindler, M.

HIV-1 replication in human immune cells is independent of TAR DNA binding Protein 43 (TDP-43) expression.

PLoS ONE 9:e105478 (2014)

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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.

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