A5057733540- Inflammasome and immune disorders
- Immune Cell Function and Interaction
- HIV Research and Treatment
- Pneumocystis jirovecii pneumonia detection and treatment
- Toxoplasma gondii Research Studies
- Kawasaki Disease and Coronary Complications
- T-cell and B-cell Immunology
Washington University in St. Louis
2020-2024
Office of Infectious Diseases
2023
HIV-1 has high mutation rates and exists as mutant swarms within the host. Rapid evolution of allows virus to outpace host immune system, leading viral persistence. Approaches targeting immutable components are needed clear infection. Here, we report that caspase recruitment domain-containing protein 8 (CARD8) inflammasome senses protease activity. can evade CARD8 sensing because its remains inactive in infected cells before budding. Premature intracellular activation triggered...
While CD4+ T cell depletion is key to disease progression in people living with HIV and SIV-infected macaques, the mechanisms underlying this remain incompletely understood, most death involving uninfected cells. In contrast, SIV infection of "natural" hosts such as sooty mangabeys does not cause AIDS despite high-level viremia. Here, we report that CARD8 inflammasome activated immediately after entry by viral protease encapsulated incoming virions. Sensing activity leads rapid pyroptosis...
HIV-1 usually utilizes CCR5 as its coreceptor and rarely switches to a CXCR4-tropic virus until the late stage of infection. CCR5+CD4+ T cells are major virus-producing in viremic individuals well SIV-infected nonhuman primates. The differentiation is associated with availability IL-15, which increases during acute Here, we report that was expressed by CD4+ exhibiting effector or memory phenotypes high expression levels IL-2/IL-15 receptor common β γ chains. but not IL-7, improved survival...
Abstract Non-nucleoside reverse transcriptase inhibitors (NNRTIs) induce pyroptosis of HIV-1 infected CD4 + T cells through induction intracellular viral protease activation, which then activates the CARD8 inflammasome. Due to high concentrations NNRTIs being required for efficient activation and elimination HIV-1-infected cells, it is important elucidate ways sensitize inflammasome NNRTI-induced activation. We show that this sensitization can be done chemical inhibition negative regulator...
Abstract HIV-1 has high mutation rates and exists as mutant swarms in the host. Rapid evolution of allows virus to outpace host immune system, leading viral persistence. Novel approaches target immutable components are needed clear infection. Here we report a pattern-recognition receptor CARD8 that senses enzymatic activity protease, which is indispensable for virus. All subtypes can be sensed by despite substantial diversity. evades sensing because protease remains inactive infected cells...