Interplay of Rad51 with NF-κB pathway stimulates expression of HIV-1
dc.creator | Kaminski, R | |
dc.creator | Wollebo, HS | |
dc.creator | Datta, PK | |
dc.creator | White, MK | |
dc.creator | Amini, S | |
dc.creator | Khalili, K | |
dc.date.accessioned | 2021-01-31T17:09:14Z | |
dc.date.available | 2021-01-31T17:09:14Z | |
dc.date.issued | 2014-05-21 | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.doi | http://dx.doi.org/10.34944/dspace/5287 | |
dc.identifier.other | 24847939 (pubmed) | |
dc.identifier.uri | http://hdl.handle.net/20.500.12613/5305 | |
dc.description.abstract | Transcription from the HIV-1 promoter is controlled by a series of ubiquitous and inducible cellular proteins with the ability to enter the nucleus and interact with the promoter. A DNA sequence spanning nucleotides -120 to -80, which supports the association of the inducible NF-κB transcription factor, has received much attention. Here we demonstrate that the interplay between Rad51, a key regulator of the homologous recombination pathway of DNA repair and whose level is induced upon HIV-1 infection, with the NF-κB pathway, augments transcription of the viral promoter. Evidently, stimulation of the NF-κB pathway by PMA and/or TSA promotes association of Rad51 with the LTR DNA sequence and that the p65 subunit of NF-κB is important for this event. Our results also demonstrate that, similar to p65, Rad51 utilizes the NF-κB pathway to position itself in the nucleus as ectopic expression of an IκB mutant impedes its nuclear appearance and transcriptional activity upon the HIV-1 LTR. Treatment of peripheral blood mononuclear cells with small molecules that inhibit Rad51 activity results in greater than 50% decrease in the HIV-1 infection of cells. These observations provide evidence for the involvement of DNA repair factors in control of HIV-1 gene activation and offer a new avenue for the development of anti-viral therapeutics that affect viral gene transcription in latently infected cells. © 2014 Kaminski et al. | |
dc.format.extent | e98304-e98304 | |
dc.language.iso | en | |
dc.relation.haspart | PLoS ONE | |
dc.relation.isreferencedby | Public Library of Science (PLoS) | |
dc.rights | CC BY | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Astrocytes | |
dc.subject | Brain | |
dc.subject | Cell Nucleus | |
dc.subject | Cells, Cultured | |
dc.subject | Gene Expression Regulation, Viral | |
dc.subject | HIV Infections | |
dc.subject | HIV Long Terminal Repeat | |
dc.subject | HIV-1 | |
dc.subject | Humans | |
dc.subject | Leukocytes, Mononuclear | |
dc.subject | Mutation | |
dc.subject | Promoter Regions, Genetic | |
dc.subject | Rad51 Recombinase | |
dc.subject | Recombination, Genetic | |
dc.subject | Transcription Factor RelA | |
dc.subject | Transcriptional Activation | |
dc.title | Interplay of Rad51 with NF-κB pathway stimulates expression of HIV-1 | |
dc.type | Article | |
dc.type.genre | Journal Article | |
dc.relation.doi | 10.1371/journal.pone.0098304 | |
dc.ada.note | For Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu | |
dc.date.updated | 2021-01-31T17:09:10Z | |
refterms.dateFOA | 2021-01-31T17:09:14Z |