Plasma and PBMC miRNA Profile in sexually HIV-1 exposed seronegative individuals

background: MicroRNAs (miRNAs) are small 20- to 24-nt non-coding RNAs involved in the post-transcriptional regulation of gene expression which play important roles in several viral infections. Global expression profiles of cellular miRNAs identified alterations of specific miRNAs post-HIV infection both in vitro and in different patient cohorts; these data suggest a potential role for miRNA in pathogenesis and disease progression. We verified if natural resistance to HIV infection in seronegative individuals repeatedly exposed to HIV (HESN) could be secondary to a peculiar miRNA signature. Methods: expression levels of 84 miRNAs, selected according to their proven anti-HIV properties were analyzed by a specific miRNA array and results were confirmed by individual RT- qPCR in plasma, unstimulated PBMC and in in vitro HIV infected PBMC isolated from 40 HESN, 40 HIV seropositive subjects (HIV+) and 40 healthy controls (HC). Results: Results showed that: 1) whereas the basal PBMC miRNA profile from HESN was similar to the one observed in HC and was characterized by an increased expression of miR-138, miR-150 and miR-190, mir29a and miR223 expression was significantly upregulated in HESN alone; 2) miR-28, miR-29a, miR-150 and miR223 expression was significantly downregulated in HIV-stimulated PBMC of HESN alone; 3) miR-28, miR-29a, miR-29b, miR-29c, miR125b, miR-146, miR-150, miR-155, miR-190 and miR-382 were increased in plasma of both HESN and HIV+ compared to HC; 4) of miR-138 and miR-223 plasmatic levels are exclusively increased in HESN compared to both HIV-1+ patients and HC. conclusions: HIV exposure modifies miRNA expression even in the absence of overt infection. Because the miRNAs that are increased in HESN, i.e. miR-29a, miR-138 and miR-223 were shown to play important role in reducing HIV replication via their ability to bind the 3’ UTR of viral mRNA, the modulation of these miRNAs could represents a key protection mechanism against HIV infection.