scholarly journals Hepatitis B: progress in understanding chronicity, the innate immune response, and cccDNA protection

2016 ◽  
Vol 4 (18) ◽  
pp. 337-337 ◽  
Author(s):  
Kenichi Morikawa ◽  
Tomoe Shimazaki ◽  
Rei Takeda ◽  
Takaaki Izumi ◽  
Machiko Umumura ◽  
...  
Keyword(s):  
Immune Response ◽  
Hepatitis B ◽  
Innate Immune Response ◽  
Innate Immune

Intrahepatic innate immune response pathways are downregulated in untreated chronic hepatitis B

2017 ◽  
Vol 66 (5) ◽  
pp. 897-909 ◽  
Author(s):  
Fanny Lebossé ◽  
Barbara Testoni ◽  
Judith Fresquet ◽  
Floriana Facchetti ◽  
Enrico Galmozzi ◽  
...  
Keyword(s):  
Immune Response ◽  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Innate Immune Response ◽  
Innate Immune

scholarly journals Hepatitis B Virus and DNA Stimulation Trigger a Rapid Innate Immune Response through NF-κB

2016 ◽  
Vol 197 (2) ◽  
pp. 630-643 ◽  
Author(s):  
Masato Yoneda ◽  
Jinhee Hyun ◽  
Silvia Jakubski ◽  
Satoru Saito ◽  
Atsushi Nakajima ◽  
...  
Keyword(s):  
Immune Response ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Innate Immune Response ◽  
Innate Immune ◽  
B Virus

scholarly journals Viral DNA-Dependent Induction of Innate Immune Response to Hepatitis B Virus in Immortalized Mouse Hepatocytes

2015 ◽  
Vol 90 (1) ◽  
pp. 486-496 ◽  
Author(s):  
Xiuji Cui ◽  
Daniel N. Clark ◽  
Kuancheng Liu ◽  
Xiao-Dong Xu ◽  
Ju-Tao Guo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Innate Immune Response ◽  
Viral Gene Expression ◽  
Innate Immune ◽  
Viral Gene ◽  
Viral Dna ◽  
B Virus

ABSTRACTHepatitis 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 off viral 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.IMPORTANCEChronic infection by hepatitis B virus (HBV) afflicts hundreds of millions worldwide and is sustained by the episomal covalently closed circular (CCC) DNA in the nuclei of infected hepatocytes. Release of viral genomic DNA from cytoplasmic nucleocapsids (NCs) (NC disassembly or uncoating) is a prerequisite for its conversion to CCC DNA, which can also potentially expose the viral DNA to host DNA sensors and trigger an innate immune response. We have found that in an immortalized mouse hepatocyte cell line in which efficient CCC DNA formation was associated with enhanced exposure of nucleocapsid-associated DNA, the exposed viral DNA indeed triggered host cytoplasmic DNA sensing and an innate immune response that was able to modulate HBV gene expression and replication. Thus, HBV can, under select conditions, be recognized by the host innate immune response through exposed viral DNA, which may be exploited therapeutically to clear viral persistence.

scholarly journals Re-evaluation of hepatitis B virus clinical phases by systems biology identifies unappreciated roles for the innate immune response and B cells

Hepatology ◽  
2015 ◽  
Vol 62 (1) ◽  
pp. 87-100 ◽  
Author(s):  
Thomas Vanwolleghem ◽  
Jun Hou ◽  
Gertine van Oord ◽  
Arno C. Andeweg ◽  
A.D.M.E. Osterhaus ◽  
...  
Keyword(s):  
Immune Response ◽  
Systems Biology ◽  
Hepatitis B Virus ◽  
B Cells ◽  
Hepatitis B ◽  
Innate Immune Response ◽  
Innate Immune ◽  
B Virus
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