Identification of a Specific miRNA Profile in HIV Exposed Seronegative Individuals

Sara YAHYAEI, Mara BIASIN, Irma SAULLE, Federica GNUDI, Mariacristina DE LUCA, Karen I I TASCA, Daria TRABATTONI, Sergio LO CAPUTO, Francesco MAZZOTTA, Mario CLERICI

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
JournalJournal of Acquired Immune Deficiency Syndromes
DOIs
Publication statusE-pub ahead of print - Sep 1 2016

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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