Long-lived resting memory CD4+ T cells (TCM) are a major reservoir of latent HIV infection. We hypothesized that latent HIV-TCM cells are maintained by aberrant expression of cell survival factors, including XIAP, BIRC2/cIAP1, and beclin-1. DIABLO/SMAC mimetics are therapeutic agents that compromise cell survival by hijacking host apoptotic machinery. We found that DIABLO/SMAC mimetics (birinapant, GDC-0152, and embelin) selectively kill HIV-TCM without increasing virus production or targeting uninfected TCM. Treatment of HIV-TCM with DIABLO/SMAC mimetics promoted XIAP and BIRC2 degradation, which triggered autophagy and the formation of a cell death complex consisting of pro-apoptotic (FADD, RIPK1, RIPK3, and caspase 8) and autophagy (ATG5, ATG7, and SQSTM1) proteins. Genetic or pharmacological inhibition of autophagy induction, but not autophagy-mediated degradation, abrogated this interaction and subsequent cell death. Our findings identify a mechanism whereby DIABLO/SMAC mimetics exploit autophagy and apoptotic machinery to selectively induce killing of HIV-TCM without viral reactivation while sparing uninfected cells.
Pubmed ID: 30344003 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
NIH HIV Reagent Program has been managed under contract by American Type Culture Collection (ATCC) since 2020. ATCC shall maintain the NIH HIV Reagent Program through identification, acquisition, production, receipt, storage, maintenance, distribution and disposal of biological and chemical research organisms and materials for HIV and other infectious diseases for use in basic and translational research.
View all literature mentionsThis polyclonal targets ATG2B
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsThis monoclonal targets HLA-DR
View all literature mentionsThis monoclonal targets XIAP (3B6) Rabbit mAb
View all literature mentionsThis monoclonal targets Hsp90aa1
View all literature mentionsThis monoclonal targets ULK1 (D9D7) Rabbit mAb
View all literature mentionsThis monoclonal targets Human TNF-alpha Neutralizing (D1B4) Rabbit mAb
View all literature mentionsThis monoclonal targets RIP3
View all literature mentionsThis monoclonal targets RIP
View all literature mentionsThis monoclonal targets PARP
View all literature mentionsThis monoclonal targets MLKL
View all literature mentionsThis monoclonal targets LAMP1
View all literature mentionsThis unknown targets FasL
View all literature mentionsThis monoclonal targets FAS
View all literature mentionsThis unknown targets Human FADD
View all literature mentionsThis monoclonal targets CASP8
View all literature mentionsThis monoclonal targets c-IAP1
View all literature mentionsThis polyclonal targets Beclin-1
View all literature mentionsThis polyclonal targets ATG2A
View all literature mentionsThis monoclonal targets CD69
View all literature mentionsThis monoclonal targets CD45RO
View all literature mentionsThis monoclonal targets Human CD4
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets Ki-67
View all literature mentionsThis monoclonal targets CD62L (L-Selectin)
View all literature mentionsThis polyclonal targets beta Tubulin (HRP) - Loading Control
View all literature mentionsThis monoclonal targets SQSTM1 / p62
View all literature mentionsThis polyclonal targets STX17 antibody
View all literature mentionsA software for acquiring and analyzing flow cytometry data. The user can create plots with elements like regions, gates, statistics, markers, and annotated text. The software can also be used for batch analysis or quality control of analysis. Results can be exported and saved.
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsCell line TZM-bl is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line CEM A3.01 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line ACH-2 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCTC clone 929 is a Spontaneously immortalized cell line with a species of origin Mus musculus
View all literature mentions