Selective persistence of HIV-1-infected T cell clones can occur through immune reprogramming driven by defective, transcriptionally active proviruses.

Defective, transcriptionally active HIV-1 proviruses at specific genomic loci can reprogram CD4+ T cells toward proliferative, immune-evasive states during ART.

• Why it matters: Understanding how HIV-infected cells persist and evade immune responses is crucial for developing strategies to eradicate the viral reservoir in people on ART, as these cells contribute to ongoing immune dysregulation.
• What they did: The study examined the effects of provirus integration at the BACH2 and STAT5B genes using cellular models and primary CD4+ T cells, focusing on how proviral transcription influences host gene expression and cell fate.
• The result: Proviral transcription at BACH2 causes aberrant BACH2 protein levels, reprogramming T cells toward proliferation and immune evasion, while at STAT5B, it promotes effector-like T cell differentiation, highlighting multifaceted impacts on immune homeostasis.