DDB1 stimulates viral transcription of hepatitis B virus via HBx-independent mechanisms

Woohyun Kim, Sooyoung Lee, Yeongnam Son, Chunkyu Ko, Wang-Shick Ryu

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

HBx, a small regulatory protein of hepatitis B virus (HBV), augments viral DNA replication by stimulating viral transcription. Among numerous reported HBx-binding proteins, DDB1 has drawn attention, because DDB1 acts as a substrate receptor of the Cul4-DDB1 ubiquitin E3 ligase. Previous work reported that the DDB1-HBx interaction is indispensable for HBx-stimulated viral DNA replication, suggesting that the Cul4-DDB1 ubiquitin E3 ligase might target cellular restriction factors for ubiquitination and proteasomal degradation. To gain further insight into the DDB1-HBx interaction, we generated HBx mutants deficient for DDB1 binding (i.e., R96A, L98A, and G99A) and examined whether they support HBx-stimulated viral DNA replication. In contrast to data from previous reports, our results showed that the HBx mutants deficient for DDB1 binding supported viral DNA replication to nearly wild-type levels, revealing that the DDB1-HBx interaction is largely dispensable for HBx-stimulated viral DNA replication. Instead, we found that DDB1 directly stimulates viral transcription regardless of HBx expression. Through an HBV infection study, importantly, we demonstrated that DDB1 stimulates viral transcription from covalently closed circular DNA, a physiological template for viral transcription. Overall, we concluded that DDB1 stimulates viral transcription via a mechanism that does not involve an interaction with HBx.

Original languageEnglish
Pages (from-to)9644-9653
Number of pages10
JournalJournal of Virology
Volume90
Issue number21
DOIs
Publication statusPublished - 2016 Jan 1

Fingerprint

Hepatitis B virus
Viral DNA
DNA replication
DNA Replication
transcription (genetics)
ubiquitin-protein ligase
Ubiquitin-Protein Ligases
circular DNA
Circular DNA
mutants
Ubiquitination
regulatory proteins
Virus Diseases
binding proteins
Carrier Proteins
receptors
degradation
infection

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Kim, Woohyun ; Lee, Sooyoung ; Son, Yeongnam ; Ko, Chunkyu ; Ryu, Wang-Shick. / DDB1 stimulates viral transcription of hepatitis B virus via HBx-independent mechanisms. In: Journal of Virology. 2016 ; Vol. 90, No. 21. pp. 9644-9653.
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DDB1 stimulates viral transcription of hepatitis B virus via HBx-independent mechanisms. / Kim, Woohyun; Lee, Sooyoung; Son, Yeongnam; Ko, Chunkyu; Ryu, Wang-Shick.

In: Journal of Virology, Vol. 90, No. 21, 01.01.2016, p. 9644-9653.

Research output: Contribution to journalArticle

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