有條件複製腺病毒介導的PreS2微型抗體表達的策略具有抑制HBV

StephenW

The Strategy of Conditionally Replicating Adenovirus-Mediated PreS2 Mini-Antibody Expression Has Dual Effects of Inhibiting HBV Infection and Preventing Hepatocellular Carcinoma
         

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Authors Ye Z, Zeng S, Xu P, Liu W, Wang S, Xia X, Su C, Guo M

Received 23 December 2020

Accepted for publication 14 February 2021

Published 24 February 2021 Volume 2021:13 Pages 1869—1876

DOI https://doi.org/10.2147/CMAR.S298331

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Chien-Feng Li

Ziheng Ye,1,* Su Zeng,1,* Peipei Xu,1 Wenfei Liu,1 Shoufei Wang,1 Xiaotian Xia,1 Changqing Su,2 Minggao Guo1

1Center 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; 2Laboratory of Viral and Gene Therapy, Eastern Hepatobiliary Surgical Hospital and Institute, The Second Military Medical University, Shanghai, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Minggao Guo Email [email protected]
Changqing Su Email [email protected]

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.

StephenW

有條件複製腺病毒介導的PreS2微型抗體表達的策略具有抑制HBV感染和預防肝癌的雙重作用
         

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作者葉Z，曾S，徐平，劉W，王S，夏X，蘇C，郭敏

2020年12月23日收到

接受發表於2021年2月14日

2021年2月24日出版第2021：13卷第1869-1876頁

DOI https://doi.org/10.2147/CMAR.S298331

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由單個匿名同行評審進行評審

同行審稿人評論2

批准發表的編輯：李建峰博士

葉子恆，1，*蘇增，1，*徐佩佩，1劉文飛，1王守飛，1夏小天，1長青蘇，2明高1

1上海交通大學附屬第六人民醫院甲狀腺，甲狀旁腺，甲狀腺和疝氣外科，甲狀腺和甲狀旁腺中心；第二軍醫大學東方肝膽外科醫院和研究所病毒與基因治療實驗室2

*這些作者同等貢獻這項工作

通訊：郭明高電子郵件[email protected]
蘇長青Email [email protected]

目的：探討乙型肝炎病毒（HBV）preS2微型抗體（mPreS2）對HBV感染，HBV相關肝損傷和HBV相關肝癌發生的抑製作用。
方法：構建具有人survivin啟動子和mPreS2基因的重組腺病毒載體Ad5SVP-mPreS2。利用熒光顯微鏡檢查和TCID 50分析來確定重組腺病毒在肝癌細胞中的特異性增殖。 Western印跡分析用於確定mPreS2表達水平。酶聯免疫吸附試驗（ELISA）用於檢測HBsAg水平，以評估mPreS2對HBV感染的抑製作用。在二乙基亞硝胺（DEN）處理的HBV轉基因印跡控制區小鼠中研究了Ad5SVP-mPreS2對肝功能的保護作用和對肝癌發生的預防作用。
結果：由人類生存素啟動子調控的重組腺病毒僅在肝癌細胞而非正常肝細胞中增殖。與正常肝細胞相比，肝癌細胞中mPreS2的表達水平增加，並且mPreS2可用於識別HBV轉基因小鼠的肝細胞。 ELISA顯示，用Ad5SVP-mPreS2治療的組中HBsAg水平降低。在DEN誘發的肝損傷模型中，Ad5SVP-mPreS2對肝臟功能具有保護作用，因為其血清丙氨酸轉氨酶和天冬氨酸轉氨酶的水平較低。此外，用DEN誘導後，用Ad5SVP-mPreS2處理的HBV轉基因小鼠與未治療的小鼠相比，癌變更少，更小。
結論：有條件地複制腺病毒介導的mPreS2表達可抑制HBV感染，並對HBV轉基因小鼠的肝損傷和肝細胞癌變具有抑製作用。

StephenW

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