Identification of miRNA-mRNA crosstalk in CD4+ T cells during HIV-1 infection by integrating transcriptome analyses

Abstract

Background: HIV-1-infected long-term nonprogressors (LTNPs) are characterized by infection with HIV-1 more than 7-10years, but keeping high CD4+ T cell counts and low viral load in the absence of antiretroviral treatment, while loss of CD4+ T cells and high viral load were observed in the most of HIV-1-infected individuals with chronic progressors (CPs) However, the mechanisms of different clinical outcomes in HIV-1 infection needs to be further resolved. Methods: To identify microRNAs (miRNAs) and their target genes related to distinct clinical outcomes in HIV-1 infection, we performed the integrative transcriptome analyses in two series GSE24022 and GSE6740 by GEO2R, R, TargetScan, miRDB, and Cytoscape softwares. The functional pathways of these differentially expressed miRNAs (DEMs) targeting genes were further analyzed with DAVID. Results: We identified that 7 and 19 DEMs in CD4+ T cells of LTNPs and CPs, respectively, compared with uninfected controls (UCs), but only miR-630 was higher in CPs than that in LTNPs. Further, 478 and 799 differentially expressed genes (DEGs) were identified in the group of LTNPs and CPs, respectively, compared with UCs. Compared to CPs, four hundred and twenty-four DEGs were identified in LTNPs. Functional pathway analyses revealed that a close connection with miRNA-mRNA in HIV-1 infection that DEGs were involved in response to virus and immune system process, and RIG-I-like receptor signaling pathway, whose DEMs or DEGs will be novel biomarkers for prediction of clinical outcomes and therapeutic targets for HIV-1. Conclusions: Integrative transcriptome analyses showed that distinct transcriptional profiles in CD4+ T cells are associated with different clinical outcomes during HIV-1 infection, and we identified a circulating miR-630 with potential to predict disease progression, which is necessary to further confirm our findings in the future.