Integrated analysis of lncRNA, miRNA and mRNA profiles reveals potential lncRNA functions during early HIV infection

Lianwei Ma,Xiaoxu Han,Minghui An,Hui Zhang,Haibo Ding,Junjie Xu,Hong Shang,Yue Zhang,Bin Zhao,Hailong Li

doi:10.1186/s12967-021-02802-9

Abstract

BackgroundLong noncoding RNAs (lncRNAs) can regulate gene expression in a cis-regulatory fashion or as “microRNA sponges”. However, the expression and functions of lncRNAs during early human immunodeficiency virus (HIV) infection (EHI) remain unclear.Methods3 HAART-naive EHI patients and 3 healthy controls (HCs) were recruited in this study to perform RNA sequencing and microRNA (miRNA) sequencing. The expression profiles of lncRNAs, mRNAs and miRNAs were obtained, and the potential roles of lncRNAs were analysed based on discovering lncRNA cis-regulatory target mRNAs and constructing lncRNA–miRNA–mRNA competing endogenous RNA (ceRNA) networks. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on 175 lncRNA-associated differentially expressed (DE) mRNAs to investigate the potential functions of DE lncRNAs in ceRNA networks.ResultsA total of 242 lncRNAs, 1240 mRNAs and 21 mature known miRNAs were determined as differentially expressed genes in HAART-naive EHI patients compared to HCs. Among DE lncRNAs, 44 lncRNAs were predicted to overlap with 41 target mRNAs, and 107 lncRNAs might regulate their nearby DE mRNAs. Two DE lncRNAs might regulate their cis-regulatory target mRNAs BTLA and ZAP70, respectively, which were associated with immune activation. In addition, the ceRNA networks comprised 160 DE lncRNAs, 21 DE miRNAs and 175 DE mRNAs. Seventeen DE lncRNAs were predicted to regulate HIF1A and TCF7L2, which are involved in the process of HIV-1 replication. Twenty DE lncRNAs might share miRNA response elements (MREs) with FOS, FOSB and JUN, which are associated with both immune activation and HIV-1 replication.ConclusionsThis study revealed that lncRNAs might play a critical role in HIV-1 replication and immune activation during EHI. These novel findings are helpful for understanding of the pathogenesis of HIV infection and provide new insights into antiviral therapy.

Highlights

Human immunodeficiency virus infection (EHI) reflects the period following viral entry during which viremia bursts occur until decreasing to a stable viral load level approximately 6 months post infection [1,2,3,4,5]
We found several differentially expressed (DE) Long noncoding RNA (lncRNA) might involve in Human immunodeficiency virus 1 (HIV-1) replication and immune activation during EHI
2619 lncRNAs were only identified in the Healthy control (HC) group, 1379 lncRNAs were only identified in the EHI patients, and 13,237 lncRNAs were identified in both groups (Fig. 1a)

Summary

Introduction

Human immunodeficiency virus infection (EHI) reflects the period following viral entry during which viremia bursts occur until decreasing to a stable viral load level approximately 6 months post infection [1,2,3,4,5]. The viral reservoir is formed early in infection. It has been reported that the events occurring during EHI are critical in determining the transmission rates, the course of disease progression, and HIV-related morbidity and mortality [6]. Exploring the mechanism of HIV pathogenesis during EHI is helpful for the design of therapeutic strategies and vaccine development. The expression and functions of lncRNAs during early human immunodeficiency virus (HIV) infection (EHI) remain unclear

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Results

Discussion

Conclusion