Figure 7.

A model depicting how the GAS5-miR-21 axis controls the function and fate of CD4 T cells in PLHIV. Two crucial non-coding RNAs, GAS5 and miR-21 are differentially expressed in CD4 T cells in PLHIV. The decline in GAS5 and increase in miR-21 expressions, along with the deficiencies in crucial enzymatic proteins involved in DNA damage and repair machineries, can cause significant increases in CD4 T cell activation, senescence, apoptosis, DNA damages, and dysregulation of cytokine productions established during latent HIV infection. Importantly, interrupting this GAS5-miR-21 axis may restore T cell homeostasis and competency and resolve premature T cell aging or immune senescence. Notably, GAS5 effects on T cell exhaustion during HIV infection may be mediated by mechanism(s) beyond GAS5-miR21 mediated signaling. Bottom: Deficiencies in Top1/2a, ATM, hTERT, and TRF2 that can cause telomeric DNA damage (30–34, 36) are known to contribute to dysfunctional CD4 T cells in HIV patients.