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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Viral Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1519639
This article is part of the Research Topic Screening and Mechanistic Study of Host Factors in the Hepatitis B Virus Life Cycle: Insights into Interferon Therapy and Its Side Effects View all articles

Cholesterol Metabolism Regulator SREBP2 Inhibits HBV Replication via Suppression of HBx Nuclear Translocation

Provisionally accepted
Fan Yang Fan Yang 1Feng Hu Feng Hu 1Hongxiao Song Hongxiao Song 1Fengchao Xu Fengchao Xu 1Jing Xu Jing Xu 1Le Wang Le Wang 1Fei Wang Fei Wang 1Yujia Zhu Yujia Zhu 1Mian Huang Mian Huang 1Min Rao Min Rao 1Haichun Ma Haichun Ma 1Guangyun Tan Guangyun Tan 1,2*
  • 1 Hepatology, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, China
  • 2 Jilin University, Changchun, Hebei Province, China

The final, formatted version of the article will be published soon.

    The intricate link between cholesterol metabolism and host immune responses is well recognized, but the specific mechanisms by which cholesterol biosynthesis influences hepatitis B virus (HBV) replication remain unclear. In this study, we show that SREBP2, a key regulator of cholesterol metabolism, inhibits HBV replication by interacting directly with the HBx protein, thereby preventing its nuclear translocation. We also found that inhibiting the ER-to-Golgi transport of the SCAP-SREBP2 complex or blocking SREBP2 maturation significantly enhances HBV suppression. Notably, we demonstrate that the C-terminal domain (CTD) of SREBP2, rather than its N-terminal domain (NTD), mediates this inhibition by interacting with HBx and promoting its extracellular secretion, thus reducing nuclear HBx accumulation. These findings reveal a novel regulatory pathway that links cholesterol metabolism to HBV replication via SREBP2-mediated control of HBx localization. This insight provides a potential basis for new therapeutic strategies against HBV infection, addressing an important global health issue.

    Keywords: cholesterol metabolism, HBV Replication, SREBP2, HBx, HBV - hepatitis B virus

    Received: 30 Oct 2024; Accepted: 16 Dec 2024.

    Copyright: © 2024 Yang, Hu, Song, Xu, Xu, Wang, Wang, Zhu, Huang, Rao, Ma and Tan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Guangyun Tan, Hepatology, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, China

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