Identification of a Specific miRNA Profile in HIV Exposed Seronegative Individuals

OBJECTIVE:: MicroRNAs (miRNAs) are small non-coding RNAs involved in the post-transcriptional regulation of gene expression that play important roles in viral infections. Alterations of specific miRNAs are described in HIV infection, suggesting a role for miRNAs in pathogenesis of this disease. We verified whether a particular miRNA signature could be identified in natural resistance to HIV-1. METHODS:: Expression level of 84 miRNAs was analyzed by RT-qPCR in plasma and unstimulated PBMC of 30 seronegative individuals repeatedly exposed to HIV-1 (HESN), 30 HIV seropositive subjects (HIV+) and 30 healthy controls (HC). Results were confirmed by individual RT-qPCR in in vitro HIV-1 infected PBMC and in their cell culture medium. Dicer and Drosha expression was analyzed in basal PBMC. RESULTS:: Whereas Dicer and Drosha expression was comparable in HESN, HIV+ and HC, several miRNAs were upregulated both in HESN and HIV+ compared to HC. Furthermore, miRNA-29a and miR-223 were upregulated in both unstimulated PBMC and plasma of HESN alone; their expression was reduced upon in vitro HIV-1 infection of HESN PBMC indicating that, upon infection, they are secreted in the extracellular milieu. These results were confirmed by individual qPCR. CONCLUSIONS:: Our studies demonstrate that HIV-1 exposure modifies miRNAs expression even in the absence of productive infection. Because those miRNAs that are specifically increased only in HESN have been known to reduce HIV-1 replication, their modulation could represent an important mechanism in resistance to HIV-1 infection.