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.
Highlights
For effective replication, HIV-1 depends on a variety of host cell factors [1,2]
Was identified originally in an approach to characterize cellular factors that bind to the HIV-1 TAR DNA region
It was suggested that TAR DNA Binding Protein 43 (TDP-43) strongly binds to double-stranded TAR DNA and may repress transcription from the HIV-1 LTR [8]
Summary
HIV-1 depends on a variety of host cell factors [1,2]. On the other hand, mammalian cells express different factors which may suppress HIV- replication and are collectively termed restriction factors [3,4]. Several HIV-1 restriction factors have been identified These include the cytidine deaminase Apobec family members, which cripple HIV1 genomes by hypermutation, the nucleotide triphosphate hydrolase SamHD1, which inhibits reverse transcription, and Tetherin, suppressing release of virus particles from the cell membrane. These antiviral factors belong to the innate immune response, are mostly interferon triggered and have evolved as a result of the continuous arms race between virus and host [3]. In addition various host cell factors are known to be capable of suppressing HIV-1 expression from integrated proviruses [6] These include host transcription factors that bind to the HIV-1 LTR and block viral transcription. Identification and characterization of host cell factors having the potential to inhibit HIV-1 replication is of high relevance
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
