有条件复制腺病毒介导的PreS2微型抗体表达的策略具有抑制HBV

StephenW

The Strategy of Conditionally Replicating Adenovirus-Mediated PreS2 Mini-Antibody Expression Has Dual Effects of Inhibiting HBV Infection and Preventing Hepatocellular Carcinoma
Ziheng Ye #  1 , Su Zeng #  1 , Peipei Xu  1 , Wenfei Liu  1 , Shoufei Wang  1 , Xiaotian Xia  1 , Changqing Su  2 , Minggao Guo  1
Affiliations
Affiliations

    1
    Center of Thyroid and Parathyroid, Department of Thyroid, Parathyroid, Breast and Hernia Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China.
    2
    Laboratory of Viral and Gene Therapy, Eastern Hepatobiliary Surgical Hospital and Institute, The Second Military Medical University, Shanghai, People's Republic of China.

#
Contributed equally.

    PMID: 33658851 PMCID: PMC7917352 DOI: 10.2147/CMAR.S298331

Abstract

Aim: To investigate the inhibitory effect of hepatitis B virus (HBV) preS2 mini-antibody (mPreS2) against HBV infection, HBV-associated liver injury and HBV-associated hepatic carcinogenesis.

Methods: A recombinant adenovirus vector with the human survivin promoter and mPreS2 gene, Ad5SVP-mPreS2, was constructed. Fluorescence microscopy examination and TCID 50 analysis were utilized to determine the specific proliferation of recombinant adenovirus in liver cancer cells. Western blot analysis was used to determine the mPreS2 expression levels. Enzyme-linked immunosorbent assay (ELISA) was used to examine HBsAg levels to evaluate the inhibitory effect of mPreS2 against HBV infection. The protective effects on hepatic function and preventive effects against hepatic carcinogenesis of Ad5SVP-mPreS2 were studied in diethylnitrosamine (DEN)-treated HBV transgenic Imprinting Control Region mice.

Results: The recombinant adenovirus regulated by the human survivin promoter proliferated exclusively in liver cancer cells rather than normal liver cells. The expression levels of mPreS2 were increased in liver cancer cells compared with normal liver cells, and mPreS2 could be used to recognize liver cells from HBV transgenic mice. ELISA showed that HBsAg levels were decreased in the group treated with Ad5SVP-mPreS2. Ad5SVP-mPreS2 had a protective effect on hepatic function in a DEN-induced liver injury model because of lower serum levels of alanine transaminase and aspartate transaminase. Additionally, HBV transgenic mice treated with Ad5SVP-mPreS2 had fewer and smaller cancerous nodes after induction with DEN than untreated mice.

Conclusion: Conditionally replicating adenovirus-mediated mPreS2 expression inhibited HBV infection and had an inhibitory effect on liver injury and hepatocellular carcinogenesis in HBV transgenic mice.

Keywords: conditionally replicating adenovirus; hepatitis B virus; hepatocellular carcinoma.

© 2021 Ye et al.

StephenW

有条件复制腺病毒介导的PreS2微型抗体表达的策略具有抑制HBV感染和预防肝癌的双重作用
子恒野1，苏增1，徐佩佩1，刘文飞1，王守飞1，夏小天1，苏长青2，郭明高1
隶属关系
隶属关系

    1个
    上海交通大学附属第六人民医院甲状腺，甲状旁腺中心，甲状腺，甲状旁腺，疝气外科。
    2个
    第二军医大学东方肝胆外科医院研究所病毒与基因治疗实验室，上海

＃
贡献均等。

    PMID：33658851 PMCID：PMC7917352 DOI：10.2147 / CMAR.S298331

抽象的

目的：探讨乙型肝炎病毒（HBV）preS2微型抗体（mPreS2）对HBV感染，HBV相关肝损伤和HBV相关肝癌发生的抑制作用。

方法：构建具有人survivin启动子和mPreS2基因的重组腺病毒载体Ad5SVP-mPreS2。利用荧光显微镜检查和TCID 50分析来确定重组腺病毒在肝癌细胞中的特异性增殖。 Western印迹分析用于确定mPreS2表达水平。酶联免疫吸附试验（ELISA）用于检测HBsAg水平，以评估mPreS2对HBV感染的抑制作用。在二乙基亚硝胺（DEN）处理的HBV转基因印迹控制区小鼠中研究了Ad5SVP-mPreS2对肝功能的保护作用和对肝癌发生的预防作用。

结果：受人类生存素启动子调控的重组腺病毒仅在肝癌细胞而非正常肝细胞中增殖。与正常肝细胞相比，肝癌细胞中mPreS2的表达水平增加，并且mPreS2可用于识别HBV转基因小鼠的肝细胞。 ELISA显示，在用Ad5SVP-mPreS2治疗的组中HBsAg水平降低。在DEN诱发的肝损伤模型中，Ad5SVP-mPreS2对肝脏功能具有保护作用，因为其血清丙氨酸转氨酶和天冬氨酸转氨酶的水平较低。此外，用DEN诱导后，用Ad5SVP-mPreS2处理的HBV转基因小鼠与未治疗的小鼠相比，癌变的数量越来越少。

结论：有条件地复制腺病毒介导的mPreS2表达可抑制HBV感染，并对HBV转基因小鼠的肝损伤和肝细胞癌变具有抑制作用。

关键词：有条件复制的腺病毒；乙型肝炎病毒;肝细胞癌。

©2021 Ye等。

StephenW

https://www.dovepress.com/front_ ... novirus-mediate.pdf

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