FIG (5-6 and 7 (graphical abstract)) Telomere and ATM dynamics in CD4 T cell depletion in active and virus-suppressed HIV-1 infection

Published: 24 September 2019| Version 1 | DOI: 10.17632/22c9d4d2bs.1
Contributors:
Sushant Khanal,
Zhi Qiang Yao

Description

Fig.5. DNA damage response in HIV-infected SupT1 and CD4 T cells with or without RAL treatment. A-B) Confocal microscopy analysis of 53BP1 and TRF1 co-localization as a marker for dysfunctional telomere-induced foci (TIF) in SupT1 and primary CD4 T cells with HIV-1 infection. C-D) Representative overlaid histograms and summary data of mean fluorescence intensity (MFI) of telomere lengths in SupT1 cells or primary CD4 T cells, with or without HIV-1 infection and RAL treatment, as measured by Flow-FISH at the indicated times. Fig.6. The PI3K/ATM pathways are dysregulated in HIV-infected T cells and promote DDR and cell apoptosis. A) The microarray results of PI3K/ATM-related gene expressions in SupT1 cells with or without HIV-1 infection at day 3. B) RT-PCR analysis of p24 and ATM/AKT-related gene expressions in SupT1 cells with or without HIV-1 infection at day 3 and day 6 after HIV-1 infection. C) Array results of PI3K/ATM-related gene expressions in primary CD4 T cells with or without HIV-1 infection at day 5. D) RT-PCR analysis of p24 and ATM/AKT-related gene expressions in primary CD4 T cells at day 5 after HIV-1 infection. E) Western blot analysis of p24, ATM, CHK2, AKT, γH2AX, and PARP-1 expressions in SupT1 cells at the early (day 3) and late (day 6) phase of HIV-1 infection. F) Western blot analysis of p24, ATM, CHK2, AKT, γH2AX and PARP-1 expressions in primary CD4 cells at the early (day 3) and late (day 5) phase of HIV-1 infection. G) Western blot analysis of p24, ATM, pATM, CHK2, pCHK2, AKT, pAKT, γH2AX and PARP-1 expressions in SupT1 cells at day 6 after HIV infection and RAL treatment. H) Western blot analysis of p24, ATM, CHK2, pCHK2, AKT and pAKT expressions in primary CD4 T cells at day 5 after HIV infection and RAL treatment. Fig.7. Model of HIV-1 infection in CD4 T cells. The PI3K/ATM pathways are initially activated and then become deficient, causing telomeric DNA damage and erosion, CD4 T cell apoptosis and depletion, during HIV-1 infection. ART can partially reverse this process by inhibiting HIV-1 replication; however, PI3K/ATM pathways will remain dysregulated in these virus-suppressed, ART-treated CD4 T cells, and thus, the cells will survive but in an early apoptotic state in this setting of latent HIV-1 infection and/or inflammation.

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AIDS Immunology

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