Suppression of complement component 2 expression by hepatitis B virus contributes to the viral persistence in chronic hepatitis B patients
Suppression of complement component 2 expression by hepatitis B virus contributes to the viral persistence in chronic hepatitis B patients
复制标题
乙型肝炎病毒对补体成分 2 表达的抑制有助于慢性乙型肝炎患者的病毒持续存在
DOI：
10.1111/jvh.13319
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发表时间：
2020-05-26
影响因子：
2.5
通讯作者：
Peng, Liang
中科院分区：
文献类型：
--
作者：
Ning, Gang;Zhen, Li-Min;Peng, Liang
此前，我们通过外显子组测序发现补体成分 2 (C2) 的罕见错义突变与慢性乙型肝炎 (CHB) 相关。然而，迄今为止，人们对C2在CHB中的作用知之甚少。在本研究中，我们旨在对 C2 在 CHB 中的潜在作用进行初步探索。方法 收集2018年1月至2020年1月中山大学附属第三医院113例CHB患者和30例健康对照者的血清样本以及5例CHB患者和3例健康对照者的肝活检样本。采用HBV感染的HepG2.2.15和HepG2-NTCP细胞检测HBV感染对C2表达的影响。使用 IFN 处理的 HepG2.2.15 细胞来评估 IFN 对 C2 表达的影响。构建C2过表达或C2沉默的HepG2.2.15细胞来评估C2对HBV感染的影响。 Western blot 和 RT-qPCR 用于测量活检样本中的 C2 表达。采用ELISA法测定培养基中的HBeAg和HBsAg以及血清样品的C2。通过 RT-qPCR 测量 HBV-DNA。 GSE84044、GSE54747 和 GSE27555 是从 GEO 下载的。与健康对照相比，CHB 患者肝组织和血清中 C2 的表达显着降低，并且与 ALT、AST、Scheuer 分级和 Scheuer 分期较高的 CHB 患者相比，ALT、AST、Scheuer 分级和分期较低的 CHB 患者的 C2 表达显着升高。此外，HBV感染可通过增加Sp1的表达和减少HDAC4的表达来降低C2的表达。此外，C2可以增强IFN对HepG2.2.15细胞的抗病毒作用，并通过抑制p38-MAPK信号通路抑制HBV在HepG2.2.15细胞中的复制。总之，HBV 可能通过抑制 C2 表达来促进 CHB 患者的病毒持续存在。
Previously, we identified rare missense mutations of complement component 2 (C2) to be associated with chronic hepatitis B (CHB) by exome sequencing. However, up to now, little is known about the role of C2 in CHB. In the present study, we aimed to perform preliminary exploration about the underlying role of C2 in CHB. Serum samples from 113 CHB patients and 30 healthy controls, and liver biopsy samples from 5 CHB patients and 3 healthy controls were obtained from the Third Affiliated Hospital of Sun Yat-sen University between January 2018 and January 2020. HepG2.2.15 and HepG2-NTCP cells infected with HBV were used to examine the influence of HBV infection on C2 expression. IFN-treated HepG2.2.15 cells were used to assess the effect of IFN on C2 expression. C2-overexpressing or C2-silencing HepG2.2.15 cells were constructed to evaluate the effect of C2 on HBV infection. Western blot and RT-qPCR were used to measure C2 expression in biopsy samples. HBeAg and HBsAg in culture medium and C2 of serum samples were measured by ELISA. HBV-DNA was measured by RT-qPCR. GSE84044, GSE54747 and GSE27555 were downloaded from GEO. C2 expression in liver tissue and serum was significantly lower in CHB patients compared to healthy controls, and significantly higher C2 expression was found in CHB patients with lower ALT, AST, Scheuer grade and stages compared to CHB patients with higher ALT, AST, Scheuer grades and Scheuer stage. Besides, HBV infection could decrease C2 expression by increasing expression of Sp1 and reducing expression of HDAC4. Moreover, C2 could enhance the anti-virus effect of IFN on HepG2.2.15 cells and also inhibit HBV replication in HepG2.2.15 cells by inhibition of p38-MAPK signalling pathway. In conclusion, HBV may promote viral persistence in CHB patients by inhibiting C2 expression.