García-García Selene, Caballero-Garralda Andrea, Tabernero David, Cortese Maria Francesca, Gregori Josep, Rodriguez-Algarra Francisco, Quer Josep, Riveiro-Barciela Mar, Homs Maria, Rando-Segura Ariadna, Pacin-Ruiz Beatriz, Vila Marta, Ferrer-Costa Roser, Pumarola Tomas, Buti Maria, Rodriguez-Frias Francisco
Liver Pathology Unit, Departments of Biochemistry and Microbiology, Vall d'Hebron University Hospital, 08035 Barcelona, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain.
Biomedicines. 2022 May 21;10(5):1194. doi: 10.3390/biomedicines10051194.
Deletions in the 3' end region of the hepatitis B virus (HBV) X open reading frame () may affect the core promoter (Cp) and have been frequently associated with hepatocellular carcinoma (HCC). The aim of this study was to investigate the presence of variants with deletions and/or insertions (Indels) in this region in the quasispecies of 50 chronic hepatitis B (CHB) patients without HCC. We identified 103 different Indels in 47 (94%) patients, in a median of 3.4% of their reads (IQR, 1.3-8.4%), and 25% (IQR, 13.1-40.7%) of unique sequences identified in each quasispecies (haplotypes). Of those Indels, 101 (98.1%) caused 44 different altered stop codons, the most commonly observed were at positions 128, 129, 135, and 362 (putative position). Moreover, 39 (37.9%) Indels altered the TATA-like box (TA) sequences of Cp; the most commonly observed caused TA2 + TA3 fusion, creating a new putative canonical TATA box. Four (8%) patients developed negative clinical outcomes after a median follow-up of 9.4 (8.7-12) years. In conclusion, we observed variants with Indels in the 3' end in the vast majority of our CHB patients, some of them encoding alternative versions of HBx with potential functional roles, and/or alterations in the regulation of transcription.
乙型肝炎病毒（HBV）X开放阅读框（）3'端区域的缺失可能会影响核心启动子（Cp），并经常与肝细胞癌（HCC）相关。本研究的目的是调查50例无HCC的慢性乙型肝炎（CHB）患者准种中该区域缺失和/或插入（Indels）变异的存在情况。我们在47例（94%）患者中鉴定出103种不同的Indels，其在reads中的中位数为3.4%（四分位间距，1.3 - 8.4%），在每个准种（单倍型）中鉴定出的独特序列的25%（四分位间距，13.1 - 40.7%）。在这些Indels中，101个（98.1%）导致了44种不同的终止密码子改变，最常见的发生在第128、129、135和362位（推定位置）。此外，39个（37.9%）Indels改变了Cp的TATA样框（TA）序列；最常见的导致TA2 + TA3融合，产生一个新的推定经典TATA框。在中位随访9.4（8.7 - 12）年后，4例（8%）患者出现了不良临床结局。总之，我们在绝大多数CHB患者中观察到3'端存在Indels变异，其中一些编码具有潜在功能作用的HBx替代版本，和/或转录调控改变。
