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.
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.
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.
aDepartment of Clinical Immunology, Westmead and Blacktown Hospitals
bSydney Medical School, University of Sydney
cSchool of Medicine, University of Western Sydney, Sydney
dImmunovirology Laboratory, St Vincent's Centre for Applied Medical Research, Darlinghurst
eThe Kirby Institute, University of New South Wales, Kensington, New South Wales, Australia
Correspondence to Dr Sanjay Swaminathan, Department of Clinical Immunology, Level 2, ICPMR, Westmead Hospital, PO Box 533, Wentworthville, NSW 2145, Australia. Tel: +61 2 98456791; fax: +61 2 98913889; e-mail: firstname.lastname@example.org