Next Article in Journal
Genomic and Proteomic Characterization of Bacteriophage BH1 Spontaneously Released from Probiotic Lactobacillus rhamnosus Pen
Previous Article in Journal
Mechanistic Insights into Chemoresistance Mediated by Oncogenic Viruses in Lymphomas
Open AccessBrief Report

Nuclear Transit and HIV LTR Binding of NF-κB Subunits Held by IκB Proteins: Implications for HIV-1 Activation

1
Department of Pediatrics, Child Health Research Center, and the Pendleton Pediatric Infectious Disease Laboratory, University of Virginia, Charlottesville, VA 22908, USA
2
Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA 22908, USA
*
Author to whom correspondence should be addressed.
Current address: Sarepta Therapeutics Inc, Dublin, OH 43210, USA.
Viruses 2019, 11(12), 1162; https://doi.org/10.3390/v11121162
Received: 13 May 2019 / Accepted: 11 December 2019 / Published: 16 December 2019
(This article belongs to the Section Animal Viruses)
No effective therapy to eliminate the HIV latently infected cell reservoir has been developed. One approach, “shock and kill”, employs agents that activate HIV, subsequently killing the activated infected cells and/or virus. Shock and kill requires agents that safely and effectively activate HIV. One class of activation agents works through classical NF-κB pathways, but global NF-κB activators are non-specific and toxic. There exist two major IκBs: IκBα, and IκBε, which hold activating NF-κB subunits in the cytoplasm, releasing them for nuclear transit upon cell stimulation. IκBα was considered the main IκB responsible for gene expression regulation, including HIV activation. IκBε is expressed in cells constituting much of the latent HIV reservoir, and IκBε knockout mice have a minimal phenotype, suggesting that IκBε could be a valuable target for HIV activation and reservoir depletion. We previously showed that targeting IκBε yields substantial increases in HIV expression. Here, we show that IκBε holds c-Rel and p65 activating NF-κB subunits in the cytoplasm, and that targeting IκBε with siRNA produces a strong increase in HIV expression associated with enhanced c-Rel and p65 transit to the nucleus and binding to the HIV LTR of the activating NF-κBs, demonstrating a mechanism through which targeting IκBε increases HIV expression. The findings suggest that it may be helpful to develop HIV activation approaches, acting specifically to target IκBε and its interactions with the NF-κBs. View Full-Text
Keywords: HIV-1; latency; activation; reservoir; IκB; IκBα; IκBε; NF-κB HIV-1; latency; activation; reservoir; IκB; IκBα; IκBε; NF-κB
Show Figures

Figure 1

MDPI and ACS Style

Khan, S.Z.; Gasperino, S.; Zeichner, S.L. Nuclear Transit and HIV LTR Binding of NF-κB Subunits Held by IκB Proteins: Implications for HIV-1 Activation. Viruses 2019, 11, 1162.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop