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

Abstract

BackgroundSeveral 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.MethodsTo 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.ResultsmiRNA-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.ConclusionsThe 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.

A pilot study on the effects of probiotic supplementation on neuropsychological performance and microRNA‐29a‐c levels in antiretroviral‐treated HIV‐1‐infected patients

“…RNAs that have been shown to play a role in modulating HIV-1 infection, either directly or indirectly (Monteleone et al, 2015;Müller et al, 2016;Su, Aloi, & Garden, 2016;Swaminathan, Navas-Martín, & Martín-García, 2014).…”

MicroRNA and HIV

“…It has been observed that HIV infection causes changes in the profile of some miRNA such as miR-29a, miR-29b, miR-125b, miR-223, miR-382, miR-198, etc. This changes have been observed in infected CD4 + T cell, PBMCs or serum [1][2][3]6,[8][9][10][19][20][21]. However, it should be taken into account that miRNAs may be regulated in different ways providing different profiles depending on the different immune compartments.…”

“…In plants, invertebrates and mammals it has been described that miRNAs play a crucial role in innate antiretroviral defense [10]. There are few described miRNAs having a direct effect on the virus but large numbers of them affect HIV indirectly throughout the regulation of factors that are necessary for viral cycle [1,2,6,[8][9][10]19,21].…”

“…miRNAs have been used as biomarkers because they are stable, present in plasma, and their detection is easy [8]. It has been demonstrated that their analysis allows to know the immune status of patients with cancer or viral infections [2,3,9,10]. miRNAs are involved in different cellular processes (differentiation, development, death) and their deregulation is related to infectious diseases, cancer or altered immune response [4,[10][11][12].…”

“…miR-29 can bind directly to 3' UTR of viral mRNA, inhibiting virus protein translation and virus replication [4,9,10,19]. miR-149 joins to vpr gene, which is involved in the transport of proviral DNA to the nucleous [4].…”