Chen Zhangming, Zhu Mengying, Pan Xiang, Zhu Yongji, Yan Hai, Jiang Tongcui, Shen Yujun, Dong Xiaowan, Zheng Nan, Lu Jinsen, Ying Songcheng, Shen Yuxian
Department of Immunology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui Province 230032, China.
School of Basic Medical Sciences and Biopharmaceutical Research Institute, Anhui Medical University, Hefei, Anhui Province 230032, China.
Biochem Biophys Res Commun. 2014 Aug 8;450(4):1462-8. doi: 10.1016/j.bbrc.2014.07.023. Epub 2014 Jul 11.
Sterile alpha motif and HD-domain containing protein 1 (SAMHD1) is a newly identified intracellular antiviral factor. By depleting the dNTPs pool of host cells to a low level that cannot support the efficient synthesis of viral cDNA, it restricts replication of some retroviruses. As a DNA virus, Hepatitis B virus (HBV) experiences a process of reverse transcription in its life cycle akin to that of retroviruses. However, whether SAMHD1 can restrict HBV replication in liver cells is unknown. Here, we reported that SAMHD1 expression was detectable in four liver cell lines. Exogenous expression of SAMHD1 in SMMC-7721 cells restrained HBV replication. Similarly, SAMHD1 impeded HBV replication in another liver cell line, BEL-7402. Remarkably, the catalytically inactive mutant, SAMHD1 HD/AA also hampered HBV replication. Additionally, HBV replication reduced SAMHD1 expression in HepG2 cells. Moreover, it was found that IFN-α induced expression of SAMHD1 in liver cells. Together, these findings suggested that IFN-α-inducible SAMHD1 inhibited HBV replication in liver cells.
含 sterile alpha 基序和 HD 结构域蛋白 1（SAMHD1）是一种新发现的细胞内抗病毒因子。它通过将宿主细胞的 dNTP 池消耗至无法支持病毒 cDNA 高效合成的低水平，从而限制某些逆转录病毒的复制。作为一种 DNA 病毒，乙型肝炎病毒（HBV）在其生命周期中经历类似于逆转录病毒的逆转录过程。然而，SAMHD1 是否能限制 HBV 在肝细胞中的复制尚不清楚。在此，我们报道在四种肝细胞系中可检测到 SAMHD1 的表达。SAMHD1 在 SMMC - 7721 细胞中的外源性表达抑制了 HBV 的复制。同样，SAMHD1 在另一种肝细胞系 BEL - 7402 中也阻碍了 HBV 的复制。值得注意的是，催化失活突变体 SAMHD1 HD/AA 也阻碍了 HBV 的复制。此外，HBV 的复制降低了 HepG2 细胞中 SAMHD1 的表达。而且，发现 IFN-α 可诱导肝细胞中 SAMHD1 的表达。总之，这些发现表明 IFN-α 诱导的 SAMHD1 抑制了 HBV 在肝细胞中的复制。
