MicroRNA modulation of key targets associated with T cell exhaustion in HIV-1 infection

Purpose of review: The emergence of studies linking microRNAs (miRNAs), a species of small RNA molecules important in gene regulation, with HIV-1 infection has led to a better understanding of the complex molecular changes that occur following infection. We aim to discuss these changes and show how miRNAs may be involved with regulating key immunomodulatory molecules linked to T cell exhaustion at the post-transcriptional level. Recent findings: Blimp-1 is a recently described T cell exhaustion marker. Reduced levels of miR-9 have been shown to have a functional role in the higher levels of Blimp-1 in CD4+T cells from patients with HIV-1 infection. Reduced levels of let-7 miRNAs have been linked to higher levels of IL-10, again with potential pathophysiological significance in HIV-1 infection. The advent of deep sequencing technologies is allowing detection of virally derived miRNAs expressed at extremely low levels, although some controversy still exists. Summary: miRNAs have emerged as important players in the T cell dysfunction observed with HIV-1 infection. It is likely that they may emerge as novel markers of T cell dysfunction and provide potential targets for new therapeutics to reverse dysfunction.