Viral DNA-dependent induction of innate immune response to hepatitis B virus in immortalized mouse hepatocytes

Xiuji Cui, Daniel N. Clark, Kuancheng Liu, Xiao Dong Xu, Ju Tao Guo, Jianming Hu

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Hepatitis B virus (HBV) infects hundreds of millions of people worldwide and causes acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. HBV is an enveloped virus with a relaxed circular (RC) DNA genome. In the nuclei of infected human hepatocytes, conversion of RC DNA from the incoming virion or cytoplasmic mature nucleocapsid (NC) to the covalently closed circular (CCC) DNA, which serves as the template for producing all viral transcripts, is essential to establish and sustain viral replication. A prerequisite for CCC DNA formation is the uncoating (disassembly) of NCs to expose their RC DNA content for conversion to CCC DNA. We report here that in an immortalized mouse hepatocyte cell line, AML12HBV10, in which RC DNA exposure is enhanced, the exposed viral DNA could trigger an innate immune response that was able to modulate viral gene expression and replication. When viral gene expression and replication were low, the innate response initially stimulated these processes but subsequently acted to shut offviral gene expression and replication after they reached peak levels. Inhibition of viral DNA synthesis or cellular DNA sensing and innate immune signaling diminished the innate response. These results indicate that HBV DNA, when exposed in the host cell cytoplasm, can function to trigger an innate immune response that, in turn, modulates viral gene expression and replication.

Original languageEnglish (US)
Pages (from-to)486-496
Number of pages11
JournalJournal of virology
Volume90
Issue number1
DOIs
StatePublished - Jan 1 2016

Fingerprint

circular DNA
Circular DNA
Hepatitis B virus
Viral DNA
Innate Immunity
hepatocytes
Hepatocytes
mice
DNA
Viral Genes
Gene Expression
gene expression
chronic hepatitis
Nucleocapsid
nucleocapsid
hepatoma
Chronic Hepatitis
virus replication
innate immunity
virion

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Cui, Xiuji ; Clark, Daniel N. ; Liu, Kuancheng ; Xu, Xiao Dong ; Guo, Ju Tao ; Hu, Jianming. / Viral DNA-dependent induction of innate immune response to hepatitis B virus in immortalized mouse hepatocytes. In: Journal of virology. 2016 ; Vol. 90, No. 1. pp. 486-496.
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Viral DNA-dependent induction of innate immune response to hepatitis B virus in immortalized mouse hepatocytes. / Cui, Xiuji; Clark, Daniel N.; Liu, Kuancheng; Xu, Xiao Dong; Guo, Ju Tao; Hu, Jianming.

In: Journal of virology, Vol. 90, No. 1, 01.01.2016, p. 486-496.

Research output: Contribution to journalArticle

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