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Hepatitis B Virus X Protein Upregulates Intracellular Calcium Signaling by Binding C-terminal of Orail Protein

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Abstract

Hepatitis B virus X (HBx) protein plays a pivotal role in the development of hepatitis B virus (HBV)-associated hepatocellular carcinoma. Although regulation of cytosolic calcium is essential for HBV replication and is mediated by HBx protein, the mechanism of HBx protein regulating intracellular calcium level remains poorly understood. The present study examined whether HBx protein elevated the intracellular calcium through interacting with storeoperated calcium entry (SOCE) components, Orail and stromal interaction molecule 1, and then identified the targets of HBx protein, with an attempt to understand the mechanism of HBx protein upsetting intracellular calcium homeostasis. By employing co-immunoprecipitation and GST-pull-down assay, we found that Orail protein interacted with HBx protein, and the C-terminus of Orail was implicated in the interaction. Confocal microscopy also revealed that HBx protein could co-localize with full-length Orail protein in HEK293 cells. Moreover, live cell calcium imaging exhibited that HBx protein elevated intracellular calcium, possibly by binding to SOCE components. Our results suggest that HBx protein binds to STIM1-Orail complexes to positively regulate the activity of plasma membrane store-operated calcium channels.

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Authors and Affiliations

  1. Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Jing-hong Yao  (姚景宏), Jian-hua Yi  (易建华) & Ya-nan Liu  (刘亚男)

  2. Department of Anatomy, School of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Zi-jian Liu  (刘子建)

  3. Department of Gastroenterology, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, China

    Jun Wang  (王 君)

Authors
  1. Jing-hong Yao  (姚景宏)
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  2. Zi-jian Liu  (刘子建)
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  3. Jian-hua Yi  (易建华)
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  4. Jun Wang  (王 君)
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  5. Ya-nan Liu  (刘亚男)
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Corresponding author

Correspondence to Zi-jian Liu  (刘子建).

Additional information

This project was supported by grants from the National Natural Science Foundation of China (No. 81001063) and the Fundamental Research Funds for the Central Universities (No. 2015QN150).

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Yao, Jh., Liu, Zj., Yi, Jh. et al. Hepatitis B Virus X Protein Upregulates Intracellular Calcium Signaling by Binding C-terminal of Orail Protein. CURR MED SCI 38, 26–34 (2018). https://doi.org/10.1007/s11596-018-1843-z

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  • DOI: https://doi.org/10.1007/s11596-018-1843-z

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