Shofa Maya, Fukushima Yuri V, Saito Akatsuki
Department of Veterinary Science, Faculty of Agriculture, University of Miyazaki, Miyazaki, Miyazaki 889-2192, Japan.
Graduate School of Medicine and Veterinary Medicine, University of Miyazaki, Miyazaki, Miyazaki 889-1692, Japan.
Int J Mol Sci. 2025 Jul 15;26(14):6786. doi: 10.3390/ijms26146786.
Hepatitis B virus (HBV), belonging to the genus , can cause chronic hepatitis and hepatocarcinoma in humans. HBV ensures optimal replication by encoding X, a multifunctional protein responsible for degrading the structural maintenance of chromosomes (Smc) 5/6 complex, an anti-HBV factor in hepatocytes. Previous studies suggest that degradation of the Smc5/6 complex is conserved among viruses from the genus . Recently, a novel hepadnavirus in cats, domestic cat HBV (DCHBV), has been identified as genetically close to HBV. However, it remains unclear whether the DCHBV X protein possesses similar Smc5/6 complex-degrading properties. Here, we investigated the degradation of the Smc5/6 complex by X proteins from viruses of the genus , including DCHBV, in cells derived from primates and cats. We found that the DCHBV X protein degraded the Smc5/6 complex in the cells of several host species, and the degree of its anti-Smc5/6 complex activity differed depending on the host species. Furthermore, the DCHBV X protein degraded Smc6 independently of DNA-binding protein 1 (DDB1), which is a critical host factor for HBV X-mediated Smc6 degradation. Our findings highlight the conserved yet divergent degradation machinery for Smc6 of mammalian hepatitis B virus X proteins.
乙型肝炎病毒（HBV）属于 属，可导致人类慢性肝炎和肝癌。HBV通过编码X蛋白来确保最佳复制，X蛋白是一种多功能蛋白，负责降解染色体结构维持（Smc）5/6复合物，该复合物是肝细胞中的一种抗HBV因子。先前的研究表明，Smc5/6复合物的降解在 属病毒中是保守的。最近，一种新发现的猫科动物肝炎病毒，家猫HBV（DCHBV），被确定在基因上与HBV接近。然而，DCHBV X蛋白是否具有类似的Smc5/6复合物降解特性仍不清楚。在这里，我们研究了包括DCHBV在内的 属病毒的X蛋白在灵长类动物和猫来源的细胞中对Smc5/6复合物的降解情况。我们发现，DCHBV X蛋白在几种宿主物种的细胞中降解了Smc5/6复合物，并且其抗Smc5/6复合物活性的程度因宿主物种而异。此外，DCHBV X蛋白独立于DNA结合蛋白1（DDB1）降解Smc6，DDB1是HBV X介导的Smc6降解的关键宿主因子。我们的研究结果突出了哺乳动物乙型肝炎病毒X蛋白对Smc6的保守但有差异的降解机制。
