Science · 2021 · 156 citations · 41 references
Life SciencesImmunologyInfectious DiseasesAdaptive ImmunityInnate ImmunityMolecular VirologyAntiviral ImmunityInflammasome ActivationInnate Immune Signaling PathwaysT Cell ActivationViral Immune EvasionViral PathogenesisCd4 Positive T CellsInflammasome Activation In Viral InfectionInflammasome Sensor ProteinsIntracellular ActivationViral Persistence MechanismsViral Protease FunctionViral ProteasesWithin-host Pathogen Diversity
Eradicating the last vestiges of HIV After treatment with antiretroviral therapy, HIV-1 wild-type and escape variants can persist in a latent form, especially within CD4 + T cells, hindering efforts to eradicate the virus. Q. Wang et al. found that human CARD8, a member of the caspase recruitment domain (CARD)–containing family of innate immune sensors, is activatable by direct proteolysis of its N-terminus by HIV-1 protease. This cleavage should result in the programmed cell death of infected cells, but HIV-1 protease remains inactive and undetected as a subunit of the unprocessed Gag-Pol polyprotein. However, when infected cells were treated with non-nucleoside reverse transcriptase inhibitors, intracellular Gag-Pol dimerization was enhanced, resulting in CARD8-mediated caspase activation and pyroptosis. Targeting this pathway may be a promising way to eliminate residual HIV-1 in patients. Science , this issue p. eabe1707
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Antibody neutralization and escape by HIV-1
Xiping Wei, Julie M. Decker, Shuyi Wang et al. · Nature · 2003 · 2.4K citations