Background Currently, there are approximately 240 million individuals worldwide suffering from chronic hepatitis B infection, yet a definitive cure remains elusive. In the context of pharmaceutical interventions for this patient population, the potential issue of Hepatitis B virus (HBV) reactivation must be taken into consideration. Nutlin-3 is a small molecule of imidazoline analog, which inhibits tumor growth by suppressing the interaction between human double minute 2 (HDM2) and p53. However, whether it affects HBV replication is not clear. Methods HepG2.2.15 cells were used to assess the impact of Nutlin-3 on HBV replication. The expression of Hepatitis B surface antigen (HBsAg) and Hepatitis B e antigen (HBeAg) was detected by ELISA. The expression of pregenomic RNA (pgRNA) and core-DNA was detected by RT-qPCR. The activation of relevant signaling pathways was assessed through Western blotting and confocal microscopy detection of the expression of associated proteins. Results We found that Nutlin-3 significantly enhances the expression of HBsAg and HBeAg, and it also promotes the expression of pgRNA and Core-DNA. Nutlin-3 promotes HBV replication independent of the HDM2. Instead, it activates the autophagy pathway through p53-mediated mTOR inhibition to promote HBV replication. Conclusion When using Nutlin-3 for cancer therapy, it’s important to be aware of the potential side effect of promoting HBV replication in individuals with chronic hepatitis B infection.

Shaowei Han

Yuanyuan Li

Junnan Wang

Yong Zhang

Acta Virologica

ACTA VIROLOGICA 是一份以分子和细胞病毒学为主的国际期刊。 ACTA VIROLOGICA 旨在发表论文，报告主要在细胞和分子水平上对人类、动物和植物病毒的基础和应用研究的原始结果。按照传统，立克次体也包括在内。感兴趣的领域是病毒结构和形态、病毒-细胞相互作用的分子生物学、病毒的分子遗传学、病毒疾病的发病机制、病毒免疫学、疫苗、抗病毒药物和病毒诊断。

Acta Virologica is an international journal focused on molecular and cellular virology. The journal aims to publish original research papers reporting fundamental and applied studies on human, animal, and plant viruses, particularly at the cellular and molecular levels. Traditionally, rickettsiae are also included in the scope of the journal. Areas of interest include virus structure and morphology, molecular biology of virus-cell interactions, molecular genetics of viruses, pathogenesis of viral diseases, virology immunology, vaccines, antiviral drugs, and viral diagnostics.

《Acta Virologica》是一本国际期刊，专注于分子和细胞病毒学。该期刊旨在发表关于人类、动物和植物病毒的基础和应用研究的原创论文，特别是在细胞和分子层面上的研究成果。根据传统，立克次体也被纳入研究范围。感兴趣的研究领域包括病毒的结构与形态、病毒与细胞相互作用的分子生物学、病毒的分子遗传学、病毒疾病的发病机制、病毒免疫学、疫苗、抗病毒药物以及病毒诊断等。

Category	Quartile
医学	4
医学, 病毒学	4

Nutlin-3 promotes HBV replication by activating mTOR-mediated autophagy

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