Genomic analysis of the host response to hepatitis B virus infection

Wieland, Stefan; Thimme, Robert; Purcell, Robert H.; Chisari, Francis V.

doi:10.1073/pnas.0401771101

Cited by 614 publications

(607 citation statements)

References 45 publications

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“…When the infection is self-limited, HBV-DNA rapidly decreases before the alanine aminotransferase (ALT) level peaks by the 12th-16th week [6]. A similar process was observed following inoculation of a chimpanzee with HBV: prior to maximum ALT level, the amount of HBV-DNA fell by more than 80 % within 2-3 weeks after the peak of viral replication [7]. This early virus control is probably sustained by non-cytopathic mechanisms [8].…”

Section: Innate Immunity In Hbv Infection: the Role Of Nk Cells And Dcsmentioning

confidence: 72%

“…As mentioned in the ''Introduction'', the first line of non-cytopathic defense is considered to be regulated by IFN-a/b, IFN-k, IFN-c and by the ISGs. However, comprehensive gene expression analyses in a chimpanzee and woodchuck infected with HBV were unable to detect measurable IFNs or ISGs during the HBV entry and expansion phase, suggesting that HBV remains largely undetected by the innate immune system [7]. Intrahepatic HBV-specific CD8 ?…”

Section: Innate Immunity In Hbv Infection: the Role Of Nk Cells And Dcsmentioning

confidence: 99%

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Host–virus interactions in hepatitis B and hepatitis C infection

Yoshio

Kanto

2016

J Gastroenterol

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Hepatitis B virus (HBV) and hepatitis C virus (HCV) are among the most endemic pathogens worldwide, with more than 500 million people globally currently infected with these viruses. These pathogens can cause acute and chronic hepatitis that progress to liver cirrhosis or hepatocellular carcinoma. Both viruses utilize multifaceted strategies to evade the host surveillance system and fall below the immunological radar. HBV has developed specific strategies to evade recognition by the innate immune system and is acknowledged to be a stealth virus. However, extensive research has revealed that HBV is recognized by dendritic cells (DCs) and natural killer (NK) cells. Indoleamine-2, 3-dioxygenase is an enforcer of sequential immune reactions in acute hepatitis B, and this molecule has been shown to be induced by the interaction of HBV-infected hepatocytes, DCs, and NK cells. The interleukin-28B genotype has been reported to influence HCV eradication either therapeutically or spontaneously, but the biological function of its gene product, a type-III interferon (IFN-k3), remains to be elucidated. Human BDCA3 ? DCs have also been shown to be a potent producer of IFN-k3 in HCV infection, suggesting the possibility that BDCA3 ? DCs could play a key role in developing therapeutic HCV vaccine. Here we review the current state of research on immune responses against HBV and HCV infection, with a specific focus on innate immunity. A comprehensive study based on clinical samples is urgently needed to improve our understanding of the immune mechanisms associated with viral control and thus to develop novel immune modulatory therapies to cure chronic HBV and HCV infection.

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Section: Innate Immunity In Hbv Infection: the Role Of Nk Cells And Dcsmentioning

confidence: 72%

Section: Innate Immunity In Hbv Infection: the Role Of Nk Cells And Dcsmentioning

confidence: 99%

Host–virus interactions in hepatitis B and hepatitis C infection

Yoshio

Kanto

2016

J Gastroenterol

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“…This hypothesis should now be tested in appropriate experimental settings, including human hepatocyte chimeric mice and in HBV-infected chimpanzees, where gene-expression analyses so far have failed to detect an up-regulation of APOBEC3 mRNA expression during viral clearance. 5 …”

mentioning

confidence: 99%

“…2 Interferons restrict the replication of HBV by inducing the expression of antiviral proteins that inhibit the formation of replication-competent HBV nucleocapsids, and ultimately can result in the resolution of the chronic HBV infection. [2][3][4][5][6][7] HBV and other hepadnaviruses replicate their partially double-stranded DNA genome within cytoplasmic core particles by reverse transcription of encapsidated pregenomic RNA and thus are related to retroviruses. 8,9 The cytidine deaminase APOBEC3G (A3G), which is encoded within a cluster of seven related editing enzymes (APOBEC3A-G) on chromosome 22, provides broad innate immunity against exogenous and endogenous retroelements.…”

mentioning

confidence: 99%

Interferon‐inducible expression of APOBEC3 editing enzymes in human hepatocytes and inhibition of hepatitis B virus replication†

et al. 2006

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Hypermutations in hepatitis B virus (HBV) DNA by APOBEC3 cytidine deaminases have been detected in vitro and in vivo, and APOBEC3G (A3G) and APOBEC3F (A3F) have been shown to inhibit the replication of HBV in vitro, but the presumably low or even absent hepatic expression of these enzymes has raised the question as to their physiological impact on HBV replication. We show that normal human liver expresses the mRNAs of APOBEC3B (A3B), APOBEC3C (A3C), A3F, and A3G. In primary human hepatocytes, interferon alpha (IFN-␣) stimulated the expression of these cytidine deaminases up to 14-fold, and the mRNAs of A3G, A3F, and A3B reached expression levels of 10%, 3%, and 3%, respectively, relative to GAPDH mRNA abundance. On transfection, the full-length protein A3B L inhibited HBV replication in vitro as efficiently as A3G or A3F, whereas the truncated splice variant A3B S and A3C had no effect. A3B L and A3B S were detected predominantly in the nucleus of uninfected cells; however, in HBV-expressing cells both proteins were found also in the cytoplasm and were associated with HBV viral particles, similarly to A3G and A3F. T he hepatitis B virus (HBV) infects more than 350 million people worldwide and is a leading cause of end-stage liver disease and of hepatocellular carcinoma. 1 HBV is non-cytopathic for hepatocytes; however, most newly HBV infected adult patients develop acute hepatitis because of a strong immune response that clears HBV from the liver, whereas approximately 5% of newly HBV-infected adult patients generate insufficient immunity and become chronically infected. 1,2 Administration of interferon alpha (IFN-␣) is a mainstay of therapy for chronically HBV-infected patients. 2 Interferons restrict the replication of HBV by inducing the expression of antiviral proteins that inhibit the formation of replication-competent HBV nucleocapsids, and ultimately can result in the resolution of the chronic HBV infection. 2-7 HBV and other hepadnaviruses replicate their partially double-stranded DNA genome within cytoplasmic core particles by reverse transcription of encapsidated pregenomic RNA and thus are related to retroviruses. 8,9 The cytidine deaminase APOBEC3G (A3G), which is encoded within a cluster of seven related editing enzymes (APOBEC3A-G) on chromosome 22, provides broad innate immunity against exogenous and endogenous retroelements. 10-16 Encapsidated into the retroviral particle A3G deaminates dCs of the retroviral minus strand

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“…27,28 We used woodchuck hepatocytes as cytotoxic effectors to facilitate future investigations on their potential involvements in the liver innate immunity and the development of different forms and outcomes of viral hepatitis. In addition, because of the critical role of intrahepatic IFN-␥ and tumor necrosis factor alpha (TNF-␣) in the recovery from or progression to chronic viral hepatitis, 29,30 the effect of these cytokines on hepatocyte-mediated cell killing was investigated.…”

mentioning

confidence: 99%