1887

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Volume 102, Issue 12

Hepatitis C virus core protein inhibits hepatitis B virus replication by downregulating HBx levels via Siah-1-mediated proteasomal degradation during coinfection No Access

Abstract

Most clinical and experimental studies have suggested that hepatitis C virus (HCV) is dominant over hepatitis B virus (HBV) during coinfection, although the mechanism remains unclear. Here, we found that HCV core protein inhibits HBV replication by downregulating HBx levels during coinfection in human hepatoma cells. For this effect, HCV core protein increased reactive oxygen species levels in the mitochondria and activated the ataxia telangiectasia mutated-checkpoint kinase two pathway in the nucleus, resulting in an upregulation of p53 levels. Accordingly, HCV core protein induced p53-dependent activation of seven in absentia homolog one expression, an E3 ligase of HBx, resulting in the ubiquitination and proteasomal degradation of HBx. The effect of the HCV core protein on HBx levels was accurately reproduced in both a 1.2-mer HBV replicon and HBV infection systems, providing evidence for the inhibition of HBV replication by HCV core protein. The present study may provide insights into the mechanism of HCV dominance in HBV- and HCV-coinfected patients.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): Core , HBx , Hepatitis B virus , hepatitis C virus , p53 and seven in absentia homolog 1
Funding
This study was supported by the:
  • National Research Foundation of Korea (Award NRF-2019R1A2C2011478)
    • Principle Award Recipient: KyungLib Jang
© 2021 The Authors
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/content/journal/jgv/10.1099/jgv.0.001701
2021-12-09
2024-05-13
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Hepatitis C virus core protein inhibits hepatitis B virus replication by downregulating HBx levels via Siah-1-mediated proteasomal degradation during coinfection
J. Gen. Virol. 102, 001701 (2021); https://doi.org/10.1099/jgv.0.001701
/content/journal/jgv/10.1099/jgv.0.001701
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