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International Journal of Biological Macromolecules

International Journal of Biological Macromolecules

IF: 7.7
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RAB1A promotes hepatitis B virus replication by enhancing PPARα-mediated viral transcription and inducing ULK1-mediated autophagy

Published:24 July 2025 DOI: 10.1016/j.ijbiomac.2025.146301 PMID: 40714109
Chen Li , Zhenyu Zhao , Beinu Guo , Dan Xu , Sihui Li , Haihuan Tang , Bei Jia , Fahong Li , Jiming Zhang , Hecun Zou , Mengji Lu , Ailong Huang , Yong Lin

Abstract

Chronic hepatitis B virus (HBV) infection poses a significant risk for the development of hepatocellular carcinoma and remains a major public health challenge globally. RAB GTPases coordinate intracellular vesicle transport and regulate various stages of the HBV life cycle. However, the influences of RAB1A on HBV replication are not well understood. In this study, we aim to elucidate the role of RAB1A in HBV replication and to explore its potential underlying mechanisms. Our study indicated that RAB1A mRNA and protein levels were significantly elevated in liver tissue samples from patients with chronic HBV infection, as well as in HBV-expressing hepatoma cells. Silencing of RAB1A markedly inhibited HBV replication and transcription in HBV-transfected and -infected hepatoma cells, whereas RAB1A overexpression resulted in increased replication and transcription. Additionally, RAB1A silencing strongly inhibited HBV replication in an HBV-persistent replicating mouse model. Mechanistically, RAB1A enhanced HBV transcription by upregulating the expression of the transcription factor PPARα. Furthermore, RAB1A facilitated HBV replication by triggering ULK1-mediated autophagy by interacting with C9orf72. In conclusion, RAB1A enhances HBV replication through dual synergistic mechanisms at the transcriptional and post-transcriptional levels, positioning RAB1A as a potential novel target for the treatment of chronic HBV infection.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
GW 6471 880635-03-0 C35H36F3N3O4 136 suppliers $35.00-$3087.00
GW 6471 880635-03-0 C35H36F3N3O4 136 suppliers $35.00-$3087.00
GW 6471 880635-03-0 C35H36F3N3O4 136 suppliers $35.00-$3087.00
GW 6471 880635-03-0 C35H36F3N3O4 136 suppliers $35.00-$3087.00

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