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

Abstract

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 workCorrespondence: Minggao Guo Email [email protected] Su Email [email protected]: 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: hepatitis B virus, hepatocellular carcinoma, conditionally replicating adenovirus

Keywords

• hepatitis b virus
• hepatocellular carcinoma
• conditionally replicating adenovirus