The CARD8 inflammasome in HIV infection

Clark, Kolin M.; Pal, Prem; Kim, Josh G.; Wang, Qiankun; Shan, Liang

doi:10.1016/bs.ai.2022.11.001

Cited by 4 publications

(7 citation statements)

References 239 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To date, the only inflammasome that has been shown to play a role in HIV reservoir dynamics is CARD8 [60 ▪▪ ], reviewed in [61 ▪ ]). Structurally, CARD8 contains a C-terminal CARD domain and an N-terminal FIIND domain.…”

Section: The Card8 Inflammasome and Pyroptosismentioning

confidence: 99%

“…Upon interaction with the cognate PAMPs, the N-terminal fragment is cleaved by viral proteases and then targeted for proteasomal degradation. N-terminal degradation allows for release of the C-terminal fragment, which can oligomerize and provide a platform for caspase-1 docking [61 ▪ ].…”

Section: The Card8 Inflammasome and Pyroptosismentioning

confidence: 99%

“…The HIV protease plays a critical role in the generation of mature infectious viral particles. Through a tightly regulated process, the HIV PR sequentially cleaves the polyprotein precursors Gag and Gag-pol to generate functional subunits [61 ▪ ]. The HIV PR only becomes activated at the time of virion release from infected cells and its premature or delayed activation leads to a significant decrease in HIV infectivity [61 ▪ ].…”

Section: The Card8 Inflammasome and Pyroptosismentioning

confidence: 99%

“…Through a tightly regulated process, the HIV PR sequentially cleaves the polyprotein precursors Gag and Gag-pol to generate functional subunits [61 ▪ ]. The HIV PR only becomes activated at the time of virion release from infected cells and its premature or delayed activation leads to a significant decrease in HIV infectivity [61 ▪ ]. In HIV-infected cells, the immature protease exists as a monomer embedded in the Gag-pol polyprotein.…”

Section: The Card8 Inflammasome and Pyroptosismentioning

confidence: 99%

“…In HIV-infected cells, the immature protease exists as a monomer embedded in the Gag-pol polyprotein. Protease activation requires Gag-pol dimerization, a process that only spontaneously occurs at low rates in the cytoplasm of infected cells [61 ▪ ]. Intriguingly, a class of HIV antiretrovirals called nonnucleoside reverse transcriptase inhibitors (NNRTIs), has been shown to induce Gag-pol dimerization, resulting in premature intracellular protease activity [62].…”

Section: The Card8 Inflammasome and Pyroptosismentioning

confidence: 99%

See 4 more Smart Citations

Pharmacological approaches to promote cell death of latent HIV reservoirs

Pinzone,

Shan

2023

Current Opinion in HIV and AIDS

Self Cite

View full text Add to dashboard Cite

Purpose of review HIV requires lifelong antiviral treatment due to the persistence of a reservoir of latently infected cells. Multiple strategies have been pursued to promote the death of infected cells. Recent findings Several groups have focused on multipronged approaches to induce apoptosis of infected cells. One approach is to combine latency reversal agents with proapoptotic compounds and cytotoxic T cells to first reactivate and then clear infected cells. Other strategies include using natural killer cells or chimeric antigen receptor cells to decrease the size of the reservoir. A novel strategy is to promote cell death by pyroptosis. This mechanism relies on the activation of the caspase recruitment domain-containing protein 8 (CARD8) inflammasome by the HIV protease and can be potentiated by nonnucleoside reverse transcriptase inhibitors. Summary The achievement of a clinically significant reduction in the size of the reservoir will likely require a combination strategy since none of the approaches pursued so far has been successful on its own in clinical trials. This discrepancy between promising in vitro findings and modest in vivo results highlights the hurdles of identifying a universally effective strategy given the wide heterogeneity of the HIV reservoirs in terms of tissue location, capability to undergo latency reversal and susceptibility to cell death.

show abstract

Section: The Card8 Inflammasome and Pyroptosismentioning

confidence: 99%

Section: The Card8 Inflammasome and Pyroptosismentioning

confidence: 99%