title: Activation of HIV-1 LTR by Rad51 in microglial cells.
abstract: Infection with HIV-1 induces a variety of biological alterations to the host that are beneficial to the life cycle of the virus but may have adverse effects on the host cell. Here we demonstrate that expression of Rad51, a major component of the homologous recombination-directed DNA repair (HRR) pathway, is induced upon HIV-1 infection of microglial cells. Activation of Rad51 expression positively impacts on HIV-1 LTR transcription through a region of the viral promoter known for binding the inducible transcription factor NFκB. Rad51 showed the ability to form a complex with the p65 subunit of NFκB and regulate the level of p65 interaction with LTR DNA encompassing the κB motif. This study provides evidence for reciprocal interaction of HIV-1 and a host DNA repair protein that impacts on expression of the viral genome. These results also point to the ability of HIV-1 to recruit proteins involved in DNA repair that are necessary for retroviral DNA integration, efficient replication and prevention of viral-induced cell death.
authors.affiliation: Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: Inna
authors.initials: I
authors.lastname: Rom
authors.forename: Armine
authors.initials: A
authors.lastname: Darbinyan
authors.forename: Martyn K
authors.initials: MK
authors.lastname: White
authors.forename: Jay
authors.initials: J
authors.lastname: Rappaport
authors.forename: Bassel E
authors.initials: BE
authors.lastname: Sawaya
authors.forename: Shohreh
authors.initials: S
authors.lastname: Amini
authors.forename: Kamel
authors.initials: K
authors.lastname: Khalili
mesh_terms: D045643:DNA Repair Enzymes / Q000378:metabolism; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D017628:Microglia / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051135:Rad51 Recombinase / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000032:analysis / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D051996:Transcription Factor RelA; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D045643:DNA Repair Enzymes