Interferon alpha-inducible protein 27 (IFI27) inhibits hepatitis B virus (HBV) transcription through downregulating cellular transcription factor C/EBP-alpha

In this project, our initial goal was to identify key antiviral ISGs that inhibit HBV replication, and we found that IFI27 (also known as ISG12a) significantly suppresses HBV replication. Our study further demonstrated that IFI27 suppresses HBV transcription through promoting ubiquitination-dependent proteasomal degradation of C/EBPalpha, a cellular transcriptional activator critical for HBV transcription. In BioSample SAMN50235703-SAMN50235704, our goal was to assess the transcriptomic response to IFN-alpha treatment in hepatocyte-derived cells. HepG2-NTCP cells were either left untreated or treated with human IFN-alpha (1,000 IU/mL) for 36 hours. Total RNA was then extracted and submitted in triplicate for mRNA sequencing in the Center for Medical Genomics at Indiana University School of Medicine. Differential transcriptome analysis was conducted, and the results are presented in Figure 1 of our publication. In BioSample SAMN50181667-SAMN50181672, our objective was to identify potential host factors involved in the IFI27-mediated anti-HBV effect. To achieve this, we performed comparative transcriptomic analysis of HepG2 cells with and without IFI27 overexpression. Total RNA was extracted and submitted in triplicate for mRNA sequencing in The Health Sciences Sequencing Core at UPMC Children's Hospital. The results of this comparative transcriptomic analysis are shown in Figure 6 of our publication.

本研究初始目标为筛选可抑制乙型肝炎病毒（Hepatitis B Virus, HBV）复制的关键抗病毒干扰素刺激基因（Interferon Stimulated Genes, ISG），最终发现IFI27（又名ISG12a）可显著抑制HBV复制。本研究进一步证实，IFI27通过促进细胞转录激活因子CCAAT增强子结合蛋白α（CCAAT/enhancer-binding protein alpha, C/EBPα）的泛素化依赖型蛋白酶体降解，从而抑制HBV转录；该转录因子是HBV转录过程的关键调控因子。
在BioSample编号SAMN50235703至SAMN50235704的样本中，本研究旨在评估肝细胞来源细胞经干扰素α（Interferon-alpha, IFN-α）处理后的转录组应答变化。将HepG2-NTCP细胞分为两组：一组不予处理，另一组以1000国际单位/毫升的人源干扰素α处理36小时。随后提取总RNA，每份样本设置三次生物学重复，送至印第安纳大学医学院医学基因组学中心进行mRNA测序。本研究完成了差异转录组分析，相关结果已发表于本研究论文的图1。
在BioSample编号SAMN50181667至SAMN50181672的样本中，本研究旨在筛选参与IFI27介导抗HBV效应的潜在宿主因子。为此，我们对过表达IFI27与未过表达IFI27的HepG2细胞开展了对比转录组分析。提取总RNA后，同样设置三次生物学重复，送至匹兹堡大学医学中心儿童医院健康科学测序中心进行mRNA测序。该对比转录组分析的结果已发表于本研究论文的图6。