Abstract
BackgroundHIV-1-infected long-term nonprogressors (LTNPs) are characterized by infection with HIV-1 more than 7–10 years, 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.MethodsTo 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.ResultsWe 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.ConclusionsIntegrative 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.
Highlights
human immunodeficiency virus 1 (HIV-1)-infected long-term nonprogressors (LTNPs) are characterized by infection with HIV-1 more than 7–10 years, 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) the mechanisms of different clinical outcomes in HIV-1 infection needs to be further resolved
With at least twofold change and FDR-adjust p value of
Twelve miRNAs were higher and 7 DEMs were down-regulated in UCs, compared with CPs, whereas miR-923 that appeared to be a fragment of the 28S rRNA was removed, and miR-768-5p overlapped an annotated snoRNA (HBII-239) was not included
Summary
HIV-1-infected long-term nonprogressors (LTNPs) are characterized by infection with HIV-1 more than 7–10 years, 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) the mechanisms of different clinical outcomes in HIV-1 infection needs to be further resolved. HIV-1 infection is characterized by the loss of number and dysfunction of CD4+ T cells and exhibits remarkable differences in clinical outcomes of treatment-naïve individuals [1]. MiR-9 regulates the expression level of Blimp-1 that considered as a T cell exhaustion marker [19], and let-7 miRNAs play a regulatory role in post-transcription of an immune inhibitory molecule, IL-10 [20]. Identification of deregulated miRNA expression profiles in different clinical outcomes of HIV-1 infection may be useful for further understanding the possible mechanisms associated with disease progression, pathogenesis and immunologic control
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