1887

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Volume 99, Issue 5

Interleukin-35 stimulates hepatitis B virus transcription and replication by targeting transcription factor HNF4α Free

Abstract

Hepatitis B virus (HBV) infection is a major health problem worldwide. Interleukin-35 (IL-35) is a definite immunosuppressive cytokine belonging to the IL-12 family. Nevertheless, the role of IL-35 in HBV replication remains elusive. In this study, we found that the level of HBV DNA replicative intermediates detected by qPCR and Southern blotting analysis was significantly increased by rhIL-35 in a dose-dependent manner. Moreover, HBV 3.5 kb mRNA levels were up-regulated by rhIL-35. The HBV core protein level as well as the HBsAg and HBeAg secretion levels were also increased by rhIL-35. Moreover, a mechanistic study demonstrated that IL-35 promoted HBV replication by enhancing the HBV core promoter activity. Importantly, hepatocyte nuclear factor 4α (HNF4α) was probably the target of IL-35. Mutation of the HNF4α-binding site on HBV core promoter or silencing HNF4α abolished the enhancement of HBV replication induced by IL-35. Finally, rhIL-35 was able to increase HBV replication in HBV transgenic mice. Taken together, our findings demonstrated that IL-35 has a novel role in HBV replication.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): hepatitis B virus , hepatocyte nuclear factor 4α , interleukin-35 and replication
© 2018 The Authors
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/content/journal/jgv/10.1099/jgv.0.001050
2018-05-01
2024-04-16
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Interleukin-35 stimulates hepatitis B virus transcription and replication by targeting transcription factor HNF4α
J. Gen. Virol. 99, 645 (2018); https://doi.org/10.1099/jgv.0.001050
/content/journal/jgv/10.1099/jgv.0.001050
/content/journal/jgv/10.1099/jgv.0.001050
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