Department of Medicine, University of Udine, 33100 Udine, Italy.
Institute of Pathology, University Hospital of Udine, 33100 Udine, Italy.
Cells. 2022 Feb 16;11(4):690. doi: 10.3390/cells11040690.
After liver transplantation, HCV/HIV co-infected patients present, compared to the HCV mono-infected ones, increased HCV viral load, rapid progression to liver fibrosis and higher mortality. Liver biopsies (LB), obtained routinely 6 months after transplantation, represent a unique model to assess the early events related to graft re-infection. Here, we used miRNA sequencing of LB obtained from both HCV-and HCV/HIV-infected recipients, to identify transcriptional profiles able to explain the more severe outcome of these latter.
miRNAs of 3 healthy livers, 3 HCV-LB and 3 HCV/HIV-LB were sequenced by Illumina HiSeq2500 platform. The DIANA-miRPath v3.0 webserver and DIANA-microT-CDS algorithm (v5.0) were used to characterize the functions of differentially expressed (DE-) miRNAs, querying the KEGG and Gene Ontology-Biological Process databases.
LB obtained from infected patients were characterized, with respect to controls, by a miRNA profile related to viral infection, immune system signaling and DNA damage in HCV-induced carcinogenesis. Instead, HCV-LB and HCV/HIV-LB differed in the expression of miRNAs involved in immunological and apoptotic processes and in extracellular matrix remodeling.
liver reinfection processes are associated with early miRNA changes. Further studies are necessary to establish their prognostic role and possible actionability.
肝移植后，HCV/HIV 合并感染患者的 HCV 病毒载量增加，肝纤维化快速进展，死亡率较高，与 HCV 单感染患者相比。肝活检（LB）通常在移植后 6 个月获得，是评估与移植物再感染相关的早期事件的独特模型。在这里，我们使用来自 HCV 和 HCV/HIV 感染受者的 LB 的 miRNA 测序，来确定能够解释这些受者更严重结局的转录谱。
通过 Illumina HiSeq2500 平台对 3 个健康肝脏、3 个 HCV-LB 和 3 个 HCV/HIV-LB 的 miRNAs 进行测序。使用 DIANA-miRPath v3.0 网络服务器和 DIANA-microT-CDS 算法（v5.0）来描述差异表达（DE-）miRNAs 的功能，查询 KEGG 和基因本体生物学过程数据库。
与对照组相比，受感染患者的 LB 具有与病毒感染、免疫系统信号和 HCV 诱导的癌变中的 DNA 损伤相关的 miRNA 谱。相反，HCV-LB 和 HCV/HIV-LB 在参与免疫和凋亡过程以及细胞外基质重塑的 miRNA 表达上存在差异。
肝再感染过程与早期 miRNA 变化有关。需要进一步研究来确定它们的预后作用和可能的可操作性。
