Year: 2021
Type: article
Abstract: A recent study published in Science 1 by Wang and colleagues shows that premature activation of the HIV-1 protease leads to caspase activation and recruitment domain 8 (CARD8) inflammasome-mediated pyroptosis of infected macrophages and CD4+ T cells (Fig. 1 ). These findings might help to improve approaches aiming to eliminate the latent viral reservoirs upon HIV-1 reactivation. Fig. 1 Activation of the CARD8 inflammasome by premature, intracellular activation of the HIV-1 protease. During regular HIV-1 infection incoming capsids are uncoated at the nuclear pore or even in the nucleus, allowing the delivery of the reverse-transcribed linear dsDNA for proviral integration into the host genome. Subsequent transcription and translation lead to expression of the Gag-Pol precursor polyprotein. Assembly and oligomerization of the polyprotein in the budding virion activates the protease, which processes and matures the virion. During NNRTI therapy or artificial Gag-Pol expression, the polyprotein accumulates in the cytoplasm leading to premature viral protease activity. Subsequent cleavage of CARD8 leads to the recruitment of pro-caspase-1, generation of active caspase-1, and ultimately pyroptotic death of HIV-1-infected cells. RT reverse transcriptase, IN integrase, CA capsid protein, MA matrix protein Full size image
Authors: Konstantin M. J. Sparrer, Frank Kirchhoff
Institutions: Universität Ulm, University Hospital Ulm
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,370
OpenAlex ID: W3154873307