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HIV-1 is the causative agent of AIDS (Autoimmune Deficiency Syndrome). HIV-1 infection results in systemic CD4+ T cell depletion, thereby impairing cell-mediated immunity. MicroRNAs are short (~22 nucleotides long), endogenous single-stranded RNA molecules that regulate gene expression by binding to the 3' untranslated regions (3' UTR) of mRNA transcripts. The relation between HIV-1 infection and human miRNA expression profile has been previously investigated, and studies have shown that the virus can alter miRNA expression and vice versa. Here, we broaden the understanding of the HIV-1 infection process, and show that miRNA-186, 210 and 222 are up-regulated following HIV-1 infection of human Sup-T1 cells. As a result, the host miRNA target genes: Dicer1 (Double-Stranded RNA-Specific Endoribonuclease), HRB (HIV-1 Rev-binding protein) and HIV-EP2 (Human Immunodeficiency Virus Type I Enhancer Binding Protein 2), are down-regulated. Moreover, testing the miRNA-gene anti- correlation on the Jurkat and the HeLa-MAGI cell lines demonstrated the ability of the miRNAs to down-regulate viral expression as well. To conclude, we found that human miR-186, 210 and 222 directly regulate the human genes Dicer1, HRB and HIV-EP2, thus may be filling key roles during HIV-1 replication and miRNA biogenesis. This finding may contribute to the development of new therapeutic strategies., Competing Interests: The authors have declared that no competing interests exist.

Stress research has progressively become more integrative in nature, seeking to unfold crucial relations between the different phenotypic levels of stress manifestations. This study sought to unravel stress-induced variations in expression of human microRNAs sampled in peripheral blood mononuclear cells and further assess their relationship with neuronal and psychological indices. We obtained blood samples from 49 healthy male participants before and three hours after performing a social stress task, while undergoing functional magnetic resonance imaging (fMRI). A seed-based functional connectivity (FC) analysis was conducted for the ventro-medial prefrontal cortex (vmPFC), a key area of stress regulation. Out of hundreds of microRNAs, a specific increase was identified in microRNA-29c (miR-29c) expression, corresponding with both the experience of sustained stress via self-reports, and alterations in vmPFC functional connectivity. Explicitly, miR-29c expression levels corresponded with both increased connectivity of the vmPFC with the anterior insula (aIns), and decreased connectivity of the vmPFC with the left dorso-lateral prefrontal cortex (dlPFC). Our findings further revealed that miR-29c mediates an indirect path linking enhanced vmPFC-aIns connectivity during stress with subsequent experiences of sustained stress. The correlative patterns of miR-29c expression and vmPFC FC, along with the mediating effects on subjective stress sustainment and the presumed localization of miR-29c in astrocytes, together point to an intriguing assumption; miR-29c may serve as a biomarker in the blood for stress-induced functional neural alterations reflecting regulatory processes. Such a multi-level model may hold the key for future personalized intervention in stress psychopathology.