MicroRNA-29 family expression and its relation to antiviral immune response and viro-immunological markers in HIV-1-infected patients

BACKGROUND: Several in vitro studies suggested the microRNA-29 (miRNA-29) family is involved in regulating HIV-1 and modulating the expression of interleukin (IL)-32, an anti-HIV-1 cytokine. METHODS: To investigate the contribution of the miRNA-29 family to HIV-1 infection in vivo, we compared miRNA-29 expression in PBMC collected from 58 HIV-1-infected patients, naïve for antiretroviral therapy, and 21 gender- and age-matched HIV-1 seronegative healthy donors, using RT-Taqman assays. The relation between miRNA-29 levels and HIV-1 viro-immunological markers and the activation rate of antiviral immune response were also evaluated. In addition, we profiled miRNA-29 expression in CD4+ T lymphocytes and CD14+ monocytes collected from 5 antiretroviral treated HIV-1 infected patients. RESULTS: miRNA-29b levels were higher in HIV-1-infected patients than in the control group (p < 0.001). There were no correlations with either HIV-1 RNA levels or CD4+ T count, whereas a significant correlation was found between miRNA-29-a/c levels and integrated HIV-1 DNA (miRNA-29a: p = 0.009, r = −0.448; miRNA-29c: p = 0.029; r = −0.381). When the HIV-1-infected patients were grouped on the basis of their plasma HIV-1 RNA and CD4+ T cell count, we also found that patients expressing the lowest levels of miRNA-29c showed high viraemia, low CD4+ T cell count and high levels of integrated HIV-1 DNA. Moreover, miRNA-29b levels were correlated with those of IL-32nonα (p = 0.028; r = −0.298). Patients expressing higher levels of miRNA-29b showed lower levels of MxA, an interferon-stimulated gene, also induced by IL-32 (p = 0.006 r = −0.397). Lastly, we found that CD4+ T lymphocytes and CD14+ monocytes shared similar miRNA-29a/b/c expression patterns but the amount of miRNA-29a/b/c, IL-32 isoforms and MxA were highly variable in these two cellular subsets. CONCLUSIONS: The miRNA-29 family could influence the clinical progression of HIV-1 infection, the HIV-1 proviral load and the innate immune response against HIV-1.