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Published on: July 21, 2022
Intracellular Casp8p41 content is inversely associated with CD4 T cell count
Nathan W Cummins1, Wei Jiang, John McGinty
1Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota 55905, USA.
Insights
Caspase-8 fragment 41 (Casp8p41) levels correlate with CD4 T cell counts in HIV infection. Higher Casp8p41 indicates lower CD4 counts, suggesting its role in T cell loss during HIV.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Human immunodeficiency virus (HIV) infection leads to a decline in CD4 T cells, a hallmark of disease progression.
- The precise mechanisms driving CD4 T cell depletion in HIV remain incompletely understood.
- Caspase-8 is a key initiator of apoptosis, and its cleavage products may play a role in immune cell death.
Purpose of the Study:
- To investigate the role of Caspase-8 fragment 41 (Casp8p41), a product of procaspase 8 cleavage by HIV protease, in HIV infection.
- To determine the association between Casp8p41 levels and CD4 T cell counts in individuals with HIV.
- To evaluate Casp8p41 as a potential biomarker for CD4 T cell loss in HIV.
Main Methods:
- Measurement of Casp8p41 protein fragment levels in memory CD4 T cells from individuals with HIV.
- Cross-sectional and longitudinal analysis of the correlation between Casp8p41 content and absolute CD4 T cell counts.
- Comparison of Casp8p41 change as a predictor of CD4 T cell count change against other established markers like viral load and activated CD8 T cells.
Main Results:
- Casp8p41 content was inversely correlated with CD4 T cell count.
- Changes in Casp8p41 levels over time were significantly associated with changes in absolute CD4 T cell counts.
- The predictive power of Casp8p41 change for CD4 T cell count decline was comparable to bacterial 16s DNA levels and superior to viral load or activated CD8 T cell percentage.
Conclusions:
- Casp8p41 is a relevant mediator of CD4 T cell death during HIV infection.
- Elevated Casp8p41 levels may signify increased apoptotic activity and contribute to the immunodeficiency observed in HIV.
- Casp8p41 warrants further investigation as a potential therapeutic target or prognostic biomarker in HIV management.
Abstract:
Casp8p41 is a protein fragment generated by cleavage of procaspase 8 by human immunodeficiency virus (HIV) protease. We measured Casp8p41 content in memory CD4 T cells and analyzed the association of Casp8p41 content with CD4 T cell count, cross-sectionally and longitudinally. Casp8p41 content was inversely correlated with CD4 T cell count, and change in Casp8p41 content was associated with absolute CD4 T cell count with change over time. Casp8p41 change was a better predictor of CD4 T cell count change than activated CD8 T cell percentage or viral load and was comparable to bacterial 16s DNA levels. This suggests that Casp8p41 is a relevant mediator of CD4 T cell death during HIV infection.
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