Hepatitis B virus polymerase blocks pattern recognition receptor signaling via interaction with DDX3: Implications for immune evasion

Haifeng Wang, Wang Shick Ryu

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

Viral infection leads to induction of pattern-recognition receptor signaling, which leads to interferon regulatory factor (IRF) activation and ultimately interferon (IFN) production. To establish infection, many viruses have strategies to evade the innate immunity. For the hepatitis B virus (HBV), which causes chronic infection in the liver, the evasion strategy remains uncertain. We now show that HBV polymerase (Pol) blocks IRF signaling, indicating that HBV Pol is the viral molecule that effectively counteracts host innate immune response. In particular, HBV Pol inhibits TANK-binding kinase 1 (TBK1)/IkB kinase-ε (IKKε), the effector kinases of IRF signaling. Intriguingly, HBV Pol inhibits TBK1/IKKε activity by disrupting the interaction between IKKε and DDX3 DEAD box RNA helicase, which was recently shown to augment TBK1/IKKε activity. This unexpected role of HBV Pol may explain how HBV evades innate immune response in the early phase of the infection. A therapeutic implication of this work is that a strategy to interfere with the HBV Pol-DDX3 interaction might lead to the resolution of life-long persistent infection.

Original languageEnglish
Article numbere1000986
Pages (from-to)1-11
Number of pages11
JournalPLoS Pathogens
Volume6
Issue number7
DOIs
Publication statusPublished - 2010 Jul 1

Fingerprint

Immune Evasion
Pattern Recognition Receptors
Hepatitis B virus
Phosphotransferases
Interferon Regulatory Factors
Innate Immunity
Virus Diseases
DEAD-box RNA Helicases
Infection
Interferons
Liver

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Parasitology
  • Virology
  • Immunology
  • Genetics
  • Molecular Biology

Cite this

@article{edc10507857a487198f2ce41f10def38,
title = "Hepatitis B virus polymerase blocks pattern recognition receptor signaling via interaction with DDX3: Implications for immune evasion",
abstract = "Viral infection leads to induction of pattern-recognition receptor signaling, which leads to interferon regulatory factor (IRF) activation and ultimately interferon (IFN) production. To establish infection, many viruses have strategies to evade the innate immunity. For the hepatitis B virus (HBV), which causes chronic infection in the liver, the evasion strategy remains uncertain. We now show that HBV polymerase (Pol) blocks IRF signaling, indicating that HBV Pol is the viral molecule that effectively counteracts host innate immune response. In particular, HBV Pol inhibits TANK-binding kinase 1 (TBK1)/IkB kinase-ε (IKKε), the effector kinases of IRF signaling. Intriguingly, HBV Pol inhibits TBK1/IKKε activity by disrupting the interaction between IKKε and DDX3 DEAD box RNA helicase, which was recently shown to augment TBK1/IKKε activity. This unexpected role of HBV Pol may explain how HBV evades innate immune response in the early phase of the infection. A therapeutic implication of this work is that a strategy to interfere with the HBV Pol-DDX3 interaction might lead to the resolution of life-long persistent infection.",
author = "Haifeng Wang and Ryu, {Wang Shick}",
year = "2010",
month = "7",
day = "1",
doi = "10.1371/journal.ppat.1000986",
language = "English",
volume = "6",
pages = "1--11",
journal = "PLoS Pathogens",
issn = "1553-7366",
publisher = "Public Library of Science",
number = "7",

}

Hepatitis B virus polymerase blocks pattern recognition receptor signaling via interaction with DDX3 : Implications for immune evasion. / Wang, Haifeng; Ryu, Wang Shick.

In: PLoS Pathogens, Vol. 6, No. 7, e1000986, 01.07.2010, p. 1-11.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Hepatitis B virus polymerase blocks pattern recognition receptor signaling via interaction with DDX3

T2 - Implications for immune evasion

AU - Wang, Haifeng

AU - Ryu, Wang Shick

PY - 2010/7/1

Y1 - 2010/7/1

N2 - Viral infection leads to induction of pattern-recognition receptor signaling, which leads to interferon regulatory factor (IRF) activation and ultimately interferon (IFN) production. To establish infection, many viruses have strategies to evade the innate immunity. For the hepatitis B virus (HBV), which causes chronic infection in the liver, the evasion strategy remains uncertain. We now show that HBV polymerase (Pol) blocks IRF signaling, indicating that HBV Pol is the viral molecule that effectively counteracts host innate immune response. In particular, HBV Pol inhibits TANK-binding kinase 1 (TBK1)/IkB kinase-ε (IKKε), the effector kinases of IRF signaling. Intriguingly, HBV Pol inhibits TBK1/IKKε activity by disrupting the interaction between IKKε and DDX3 DEAD box RNA helicase, which was recently shown to augment TBK1/IKKε activity. This unexpected role of HBV Pol may explain how HBV evades innate immune response in the early phase of the infection. A therapeutic implication of this work is that a strategy to interfere with the HBV Pol-DDX3 interaction might lead to the resolution of life-long persistent infection.

AB - Viral infection leads to induction of pattern-recognition receptor signaling, which leads to interferon regulatory factor (IRF) activation and ultimately interferon (IFN) production. To establish infection, many viruses have strategies to evade the innate immunity. For the hepatitis B virus (HBV), which causes chronic infection in the liver, the evasion strategy remains uncertain. We now show that HBV polymerase (Pol) blocks IRF signaling, indicating that HBV Pol is the viral molecule that effectively counteracts host innate immune response. In particular, HBV Pol inhibits TANK-binding kinase 1 (TBK1)/IkB kinase-ε (IKKε), the effector kinases of IRF signaling. Intriguingly, HBV Pol inhibits TBK1/IKKε activity by disrupting the interaction between IKKε and DDX3 DEAD box RNA helicase, which was recently shown to augment TBK1/IKKε activity. This unexpected role of HBV Pol may explain how HBV evades innate immune response in the early phase of the infection. A therapeutic implication of this work is that a strategy to interfere with the HBV Pol-DDX3 interaction might lead to the resolution of life-long persistent infection.

UR - http://www.scopus.com/inward/record.url?scp=77955381494&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955381494&partnerID=8YFLogxK

U2 - 10.1371/journal.ppat.1000986

DO - 10.1371/journal.ppat.1000986

M3 - Article

C2 - 20657822

AN - SCOPUS:77955381494

VL - 6

SP - 1

EP - 11

JO - PLoS Pathogens

JF - PLoS Pathogens

SN - 1553-7366

IS - 7

M1 - e1000986

ER -