Effect of PLK3 inhibitors treatment on the global transcriptome of resting CD4+ T Cells [miRNA-Seq]

The persistence of HIV-1 reservoirs in resting CD4? T cells despite the administration of antiretroviral therapy (ART) remains a major barrier to achieving a cure. In this research, we identified polo-like kinase 3 (PLK3) as a host antiviral factor able to suppress HIV-1 translation by targeting rare host tRNAs—specifically, tRNA-Ile-TAT and tRNA-Leu-TAA—in resting CD4? T cells.The inhibition of PLK3 increases the production of viral proteins, including gp120 and Gag, in active reservoirs without cellular stimulation, thereby rendering infected cells vulnerable to CAR-T–mediated clearance.Together, these findings provide evidence that PLK3 is a key host regulator of HIV-1 translation in resting CD4? T cells as well as a potential therapeutic target for reservoir eradication that may lead to a functional cure. Overall design: RNA-seg profiling of CD4+T cells treated with DMSO, GW843682X, TAK-960, NMS-P937 at 24h and 48h.