Cell intrinsic innate immunity protein RPRD2 restricts transcription from the HIV-1 LTR in human cell lines

HIV-1 establishes latency after infection in resting CD4+ T-cells which prevents the host from clearing the virus. Highly active antiretroviral therapy effectively keeps HIV replication under control, however, the latent reservoir remains unaffected, thus therapy is never curative. The establishment and persistence of latency are complex and still incompletely characterised. Host factors that repress retroviral transcription are thought to be involved in this phenomenon. RPRD2 was identified as an antiviral protein that restricts HIV replication during reverse transcription. RPRD2 has since been shown as a general inhibitor of transcription. Here we show that RPRD2 might also be involved in the restriction of HIV provirus transcription. Transient siRNA knockdown of RPRD2 increases transcription in 293T cells transfected with a GFP tagged HIV-1 LTR driven reported vector. Interestingly when RPRD2 is transiently knocked down in HeLa cells there is no effect on HIV-1 LTR GFP reporter expression. Our results propose a novel role for RPRD2 in the transcriptional repression of HIV-1, which may affect viral latency. The inadequacies of antiretroviral therapy make the development of an HIV cure essential. Currently the two major cure strategies “Shock and kill” and “Block and lock” require a better understanding of latency and the transcription of the HIV-1 provirus. Studying RPRD2 in the context of transcription may be of value for the development of an HIV-1 cure.

Grantor dc:publisher

The University of Edinburgh

Year dc:date.issued

2023

Author dc:creator

• Tarcan, Arda

Advisors dc:contributor.advisor

• Sloan, Richard
• Picozzi, Kim

• HIV-1
• CD4+ T-cells
• resting CD4+ T-cells
• HIV replication
• RPRD2
• Transient siRNA
• GFP tagged HIV-1 LTR
• HIV-1 LTR GFP reporter expression
• Shock and kill
• Block and lock

Language dc:language.iso

en

Identifier URI

http://dx.doi.org/10.7488/era/5619

OAI identifier oai:identifier

oai:era.ed.ac.uk:1842/43073