Hepatitis B virus (HBV) infection is closely related with the occurrence and development of hepatocellular carcinoma (HCC), in which Hepatitis B virus x protein (HBx) and core protein (HBc) play crucial roles. Additionally, inhibitors of differentiation (Id) proteins exhibited significant correlation with liver cancer development. Here, we identified that HBV dramatically inhibited the expression of Id1 and Id3 in both protein and transcriptional levels for the first time, whereas there was little effect of the virus on Id2. Additionally, two HBV coded protein, HBc and HBx, could reduce the expression of Id1 and Id3 distinctly, whereas the other two viral proteins, HBs and HBp were unable to affect Id1 and Id3 proteins. Both the activity inhibitors and activators further confirmed that HBc inhibited the expression of Id1 and Id3 by BMP/Smad signaling pathway. HBx could interact with both Id1 and Id3 at residues 112-136 of HBx protein, and it could inhibit the two Id proteins by accelerating their degradation. This is the first report about HBc and HBx regulating Id1 and Id3, whereas the detailed mechanism associated with above needed further experiments to clarify.

中文翻译：

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乙型肝炎病毒的 HBx 和 HBc 可以通过降低 Id1 和 Id3 的转录和稳定性来影响它们。

乙型肝炎病毒（HBV）感染与肝细胞癌（HCC）的发生发展密切相关，其中乙型肝炎病毒x蛋白（HBx）和核心蛋白（HBc）起着至关重要的作用。此外，分化抑制剂 (Id) 蛋白表现出与肝癌发展的显着相关性。在这里，我们发现 HBV 首次在蛋白质和转录水平上显着抑制了 Id1 和 Id3 的表达，而病毒对 Id2 的影响很小。此外，两种HBV编码蛋白HBc和HBx可以明显降低Id1和Id3的表达，而另外两种病毒蛋白HBs和HBp不能影响Id1和Id3蛋白。活性抑制剂和激活剂均进一步证实 HBc 通过 BMP/Smad 信号通路抑制 Id1 和 Id3 的表达。HBx 可以在 HBx 蛋白的 112-136 位残基处与 Id1 和 Id3 相互作用，并且可以通过加速它们的降解来抑制这两种 Id 蛋白。这是关于 HBc 和 HBx 调节 Id1 和 Id3 的第一份报告，而与上述相关的详细机制需要进一步的实验来阐明。