CARD8 inflammasome sensitization through DPP9 inhibition enhances NNRTI-triggered killing of HIV-1-infected cells
Clark, K. M.; Wang, Q.; Shan, L.
Show abstract
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) induce pyroptosis of HIV-1 infected CD4+ T cells through induction of intracellular viral protease activation, which then activates the CARD8 inflammasome. Due to high concentrations of NNRTIs being required for efficient CARD8 activation and elimination of HIV-1-infected cells, it is important to elucidate ways to sensitize the CARD8 inflammasome to NNRTI-induced activation. We show that this sensitization can be done through chemical inhibition of the CARD8 negative regulator DPP9. DPP9 inhibitor Val-boroPro (VbP) can act synergistically with NNRTIs to increase their efficacy in killing HIV-1-infected cells. We also show that VbP is able to partially overcome issues with NNRTI resistance and is capable of killing infected cells without the presence of NNRTIs. This offers a promising strategy for enhancing NNRTI efficacy in elimination of HIV-1 reservoirs in patients.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Non-neutralizing antibodies targeting the immunogenic regions of HIV-1 envelope reduce mucosal infection and virus burden in humanized mice 96%
- Release of P-TEFb from the Super Elongation Complex promotes HIV-1 latency reversal 96%
- HIV-1 accessory protein Vpr possesses a cryptic p300-dependent transcription-promoting activity that is blocked by histone deacetylases in CD4+ T cells. 95%
Similar papers in this journal
- Induction of selective cell death in HIV-1-infected cells by DDX3 inhibitors leads to depletion of the inducible reservoir 97%
- HIV-1 Vpr combats the PU.1-driven antiviral response in primary human macrophages. 96%
- Emergence of transmissible SARS-CoV-2 variants with decreased sensitivity to antivirals in immunocompromised patients with persistent infections 96%
Similar papers in this journal
- Identification of an antiretroviral small molecule that appears to be a host-targeting inhibitor of HIV-1 assembly 97%
- A novel high throughput microwell outgrowth assay for HIV infected cells 95%
- Anti-apoptotic clone 11 derived peptides induce in vitro death of CD4+ T cells susceptible to HIV-1 infection 94%
Similar papers in this journal
- Screening a library of FDA-approved and bioactive compounds for antiviral activity against SARS-CoV-2 93%
- Challenges for targeting SARS-CoV-2 proteases as a therapeutic strategy for COVID-19 93%
- Immunogenicity and protective efficacy of a highly thermotolerant, trimeric SARS-CoV-2 receptor binding domain derivative 93%
Similar papers in this journal
- Exploiting rodent cell blocks for intrinsic resistance to HIV-1 gene expression in human T cells 94%
- HIV-1 evolutionary dynamics under non-suppressive, 2 nd -line protease-inhibitor containing antiretroviral therapy 94%
- HIV-1 Vpr-induced DNA damage activates NF-κB through ATM-NEMO independent of cell cycle arrest 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.