NHC Key Laboratory of AIDS Immunology (China Medical University), Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, No 155, Nanjing North Street, Heping District, Shenyang, 110001, Liaoning, China.
Key Laboratory of AIDS Immunology of Liaoning Province, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
J Transl Med. 2018 Nov 29;16(1):332. doi: 10.1186/s12967-018-1706-1.
The events in early HIV infection (EHI) are important determinants of disease severity and progression rate to AIDS, but the mechanisms of pathogenesis in EHI have not been fully understood. Circular RNAs (circRNAs) have been verified as "microRNA sponges" that regulate gene expression through competing endogenous RNA (ceRNA) networks, but circRNA expression profiles and their contribution to EHI pathogenesis are still unclear.
Two different libraries were constructed with RNA from human peripheral blood mononuclear cells from 3 HARRT-naive EHI patients and 3 healthy controls (HCs). The complete transcriptomes were sequenced with RNA sequencing (RNA-Seq) and miRNA sequencing (miRNA-Seq). The differentially expressed (DE) RNAs were validated with RT-qPCR. The circRNA profile and circRNA-associated-ceRNA network in EHI were analyzed with the integrated data of RNA-Seq and miRNA-Seq. Gene ontology (GO) analysis was used to annotate the circRNAs involved in the circRNA-associated-ceRNA networks.
A total of 1365 circRNAs, 30 miRNAs, and 2049 mRNAs were differentially expressed between HARRT-naive EHI patients and HCs. A ceRNA network was constructed with 516 DE circRNAs and 903 DE mRNAs that shared miR response elements with 21 DE miRNAs. GO analysis demonstrated the multiple roles of the circRNAs enriched in EHI with circRNA-associated-ceRNA networks, such as immune response, inflammatory response and defense responses to virus, 67 circRNAs were revealed to be potentially involved in HIV-1 replication through regulating the expression of CCNK, CDKN1A and IL-15.
This study, for the first time, revealed a large circRNA profile and complex pathogenesis roles of circRNAs in EHI. A group of enriched circRNAs and associated circRNA-associated-ceRNA networks might contribute to HIV replication regulation and provide novel potential targets for both the pathogenesis of EHI and antiviral therapy.
早期 HIV 感染（EHI）中的事件是决定疾病严重程度和艾滋病进展速度的重要因素，但 EHI 发病机制的机制尚未完全理解。环状 RNA（circRNA）已被验证为“miRNA 海绵”，通过竞争内源 RNA（ceRNA）网络调节基因表达，但 circRNA 表达谱及其对 EHI 发病机制的贡献仍不清楚。
使用来自 3 名未经 HARRT 治疗的 EHI 患者和 3 名健康对照（HC）的人外周血单个核细胞 RNA 构建了两个不同的文库。使用 RNA 测序（RNA-Seq）和 miRNA 测序（miRNA-Seq）对完整的转录组进行测序。使用 RT-qPCR 验证差异表达（DE）RNAs。使用 RNA-Seq 和 miRNA-Seq 的综合数据分析 EHI 中的 circRNA 谱和 circRNA 相关 ceRNA 网络。使用基因本体论（GO）分析注释参与 circRNA 相关 ceRNA 网络的 circRNA。
未经 HARRT 治疗的 EHI 患者与 HCs 之间共鉴定出 1365 个 circRNA、30 个 miRNA 和 2049 个 mRNA 存在差异表达。构建了一个 ceRNA 网络，其中包含 516 个 DE circRNA 和 903 个与 21 个 DE miRNA 共享 miR 反应元件的 DE mRNA。GO 分析表明，EHI 中富集的 circRNA 及其相关 ceRNA 网络具有多种作用，例如免疫反应、炎症反应和对病毒的防御反应，67 个 circRNA 通过调节 CCNK、CDKN1A 和 IL-15 的表达被揭示可能参与 HIV-1 复制。
本研究首次揭示了 EHI 中大量的 circRNA 谱和复杂的 circRNA 发病机制作用。一组富集的 circRNA 及其相关的 circRNA 相关 ceRNA 网络可能有助于 HIV 复制的调节，并为 EHI 的发病机制和抗病毒治疗提供新的潜在靶点。
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