DDX3 DEAD-box RNA helicase is a host factor that restricts hepatitis B virus replication at the transcriptional Level

Chunkyu Ko, Sooyoung Lee, Marc P. Windisch, Wang-Shick Ryu

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

DDX3 is a member of the DEAD-box RNA helicase family, involved in mRNA metabolism, including transcription, splicing, and translation. We previously identified DDX3 as a hepatitis B virus (HBV) polymerase (Pol) binding protein, and by using a transient transfection, we found that DDX3 inhibits HBV replication at the posttranscriptional level, perhaps following encapsidation. To determine the exact mechanism of the inhibition, we here employed a diverse HBV experimental system. Inconsistently, we found that DDX3-mediated inhibition occurs at the level of transcription. By using tetracycline-inducible HBV-producing cells, we observed that lentivirus-mediated DDX3 expression led to a reduced level of HBV RNAs. Importantly, knockdown of DDX3 by short hairpin RNA resulted in augmentation of HBV RNAs in two distinct HBV replication systems: (i) tetracyclineinducible HBV-producing cells and (ii) constitutive HBV-producing HepG2.2.15 cells. Moreover, DDX3 knockdown in HBVsusceptible HepG2-NTCP cells, where covalently closed circular DNA (cccDNA) serves as the template for viral transcription, resulted in increased HBV RNAs, validating that transcription regulation by DDX3 occurs on a physiological template. Overall, our results demonstrate that DDX3 represents an intrinsic host antiviral factor that restricts HBV transcription.

Original languageEnglish
Pages (from-to)13689-13698
Number of pages10
JournalJournal of Virology
Volume88
Issue number23
DOIs
Publication statusPublished - 2014 Jan 1

Fingerprint

DEAD-box RNA Helicases
Hepatitis B virus
Virus Replication
virus replication
transcription (genetics)
RNA
DEAD-box RNA helicases
cells
circular DNA
Virus Attachment
Circular DNA
Lentivirus
Hep G2 Cells
transfection
small interfering RNA
Tetracycline
tetracycline
Small Interfering RNA
translation (genetics)
Antiviral Agents

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

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title = "DDX3 DEAD-box RNA helicase is a host factor that restricts hepatitis B virus replication at the transcriptional Level",
abstract = "DDX3 is a member of the DEAD-box RNA helicase family, involved in mRNA metabolism, including transcription, splicing, and translation. We previously identified DDX3 as a hepatitis B virus (HBV) polymerase (Pol) binding protein, and by using a transient transfection, we found that DDX3 inhibits HBV replication at the posttranscriptional level, perhaps following encapsidation. To determine the exact mechanism of the inhibition, we here employed a diverse HBV experimental system. Inconsistently, we found that DDX3-mediated inhibition occurs at the level of transcription. By using tetracycline-inducible HBV-producing cells, we observed that lentivirus-mediated DDX3 expression led to a reduced level of HBV RNAs. Importantly, knockdown of DDX3 by short hairpin RNA resulted in augmentation of HBV RNAs in two distinct HBV replication systems: (i) tetracyclineinducible HBV-producing cells and (ii) constitutive HBV-producing HepG2.2.15 cells. Moreover, DDX3 knockdown in HBVsusceptible HepG2-NTCP cells, where covalently closed circular DNA (cccDNA) serves as the template for viral transcription, resulted in increased HBV RNAs, validating that transcription regulation by DDX3 occurs on a physiological template. Overall, our results demonstrate that DDX3 represents an intrinsic host antiviral factor that restricts HBV transcription.",
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DDX3 DEAD-box RNA helicase is a host factor that restricts hepatitis B virus replication at the transcriptional Level. / Ko, Chunkyu; Lee, Sooyoung; Windisch, Marc P.; Ryu, Wang-Shick.

In: Journal of Virology, Vol. 88, No. 23, 01.01.2014, p. 13689-13698.

Research output: Contribution to journalArticle

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