Lee HyunJoo, Kim Hong, Lee Seoung-Ae, Won You-Sub, Kim Hye-In, Inn Kyung-Soo, Kim Bum-Joon
1Department of Biomedical Sciences, Microbiology and Immunology, Liver Research Institute, and Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Korea.
2Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, Korea.
J Gen Virol. 2015 Jul;96(Pt 7):1850-4. doi: 10.1099/vir.0.000134. Epub 2015 Mar 31.
Hepatitis B virus (HBV) infection is associated with a broad spectrum of clinical manifestations, including cirrhosis and hepatocellular carcinoma (HCC). Endoplasmic reticulum (ER) stress and subsequent oxidative stress have been implicated in liver carcinogenesis and disease progression with chronic inflammation. In our previous study, several mutations in the precore/core region of HBV genotype C were identified from 70 Korean chronic patients, and the mutations were associated with HCC and/or HBV e antigen serostatus. Here, we found that the naturally occurring mutations P5T/H/L of the HBV core antigen induced ER stress. The upregulation of ER stress resulted in higher reactive oxygen species production, intracellular calcium concentration, inflammatory cytokines as well as surface antigen production and apoptosis of cells. This study suggested that these mutations may contribute to the progression of liver disease in chronic patients.
乙型肝炎病毒（HBV）感染与一系列临床表现相关，包括肝硬化和肝细胞癌（HCC）。内质网（ER）应激及随后的氧化应激与慢性炎症导致的肝癌发生和疾病进展有关。在我们之前的研究中，从70例韩国慢性患者中鉴定出了HBV C基因型前核心/核心区域的几个突变，这些突变与HCC和/或HBV e抗原血清学状态相关。在此，我们发现HBV核心抗原的天然发生突变P5T/H/L诱导了内质网应激。内质网应激的上调导致更高的活性氧产生、细胞内钙浓度、炎性细胞因子以及细胞表面抗原产生和凋亡。本研究提示这些突变可能促成慢性患者肝病的进展。
