丁型肝炎病毒(HDV),具有两种形式的δ抗原(HDAg)的RNA病毒,依赖乙型肝炎病毒(HBV)为肝细胞进入所必需的包膜蛋白。肝细胞癌(HCC)在全球癌症死亡人数中排名第三,然而HDV的参与仍不确定。在台湾国立卫生研究院的300个HBV相关肝癌血清样本中,2.7%(8/300)的抗HDV检测呈阳性,其中62.7%(5/8)的HDVRNA也呈阳性。基因分型显示一个样本中的HDV-2,HDV-4合二为一,两个样本显示HDV-2/HDV-4混合感染和RNA重组。混合基因型感染揭示了多聚腺苷酸化信号的新突变,与L-HDAg的o石终止密码子一致。为了更深入地研究台湾主要基因型HDV-2可能的致癌特性,以前被认为与严重疾病结局的相关性较小,从HCC中分离出HDV-2cDNA克隆用于研究。在转染的培养细胞中,其复制水平达到广泛使用的HDV-1菌株的74%。令人惊讶的是,两种形式的HDV-2HDAg促进细胞迁移和侵袭,影响肌动蛋白细胞骨架的重排和上皮-间质转化标志物的表达。总之,这项研究强调了HDV-2,HDV-4的患病率,以及它们在HCC中的混合感染,强调HCC的遗传多样性以及两种形式的HDAg在HCC肿瘤发生中的潜在作用。
Hepatitis delta virus (HDV), an RNA virus with two forms of the delta antigen (HDAg), relies on hepatitis B virus (HBV) for envelope proteins essential for hepatocyte entry. Hepatocellular carcinoma (HCC) ranks third in global cancer deaths, yet HDV\'s involvement remains uncertain. Among 300 HBV-associated HCC serum samples from Taiwan\'s National Health Research Institutes, 2.7% (8/300) tested anti-HDV positive, with 62.7% (5/8) of these also HDV RNA positive. Genotyping revealed HDV-2 in one sample, HDV-4 in two, and two samples showed mixed HDV-2/HDV-4 infection with RNA recombination. A mixed-genotype infection revealed novel mutations at the polyadenylation signal, coinciding with the ochre termination codon for the L-HDAg. To delve deeper into the possible oncogenic properties of HDV-2, the predominant genotype in Taiwan, which was previously thought to be less associated with severe disease outcomes, an HDV-2 cDNA clone was isolated from HCC for study. It demonstrated a replication level reaching up to 74% of that observed for a widely used HDV-1 strain in transfected cultured cells. Surprisingly, both forms of HDV-2 HDAg promoted cell migration and invasion, affecting the rearrangement of actin cytoskeleton and the expression of epithelial-mesenchymal transition markers. In summary, this study underscores the prevalence of HDV-2, HDV-4, and their mixed infections in HCC, highlighting the genetic diversity in HCC as well as the potential role of both forms of the HDAg in HCC oncogenesis.