Early kinetics of innate and adaptive immune responses during hepatitis B virus infection

Fisicaro, Paola; Valdatta, Caterina; Boni, Carolina; Massari, Marco; Mori, Cristina; Zerbini, Alessandro; Orlandini, A.; Sacchelli, Luca; Missale, Gabriele; Ferrari, Carlo

doi:10.1136/gut.2008.163600

Cited by 259 publications

(231 citation statements)

References 32 publications

(30 reference statements)

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“…Nonetheless, the lack of early intrahepatic antiviral genes induction may be peculiar to chimpanzee models, because NK and NKT cells are activated within 72 h after infection of woodchuck with WHV (woodchuck hepatitis virus), and results in transient suppression of viral replication (Guy et al, 2008). Moreover, IL-15 level and activation of NK and NKT cells are elevated during incubation phase of natural HBV infection, but tend to decline at the peak of viraemia, implying that HBV could counteract innate immune response (Dunn et al, 2009;Fisicaro et al, 2009). We have now provided evidence that production of type I IFN in response to SeV infection is dampened by HBV replication in HepG2.2.15 cells, when compared to that in HepG2 cells.…”

Section: Discussionmentioning

confidence: 99%

“…The lack of detection of immune-related genes in the liver of infected chimpanzees has led to the consideration that HBV is a stealth virus (Wieland et al, 2004). However, this view seems to be contradicted by the observation that NK and NKT cells are promptly activated before the peak of virus expansion in natural human infection (Webster et al, 2000;Dunn et al, 2009;Fisicaro et al, 2009). Therefore, strategies may have been adapted by HBV to suppress the initial defenses of innate immunity, including type I IFN response.…”

Section: Introductionmentioning

confidence: 99%

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Mechanism of inhibiting type I interferon induction by hepatitis B virus X protein

Jiang

Tang

2010

Protein Cell

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mechanism of inhibiting type I interferon induction by hepatitis B virus X protein

Jiang

Tang

2010

Protein Cell

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“…Fisicaro et al reported two intriguing cases of patients who successfully cleared HBV after the primary infection without any apparent elevation in ALT level [10]. Longitudinal immunological analyses revealed that NK cells are activated and produce IFN-c prior to the increase in HBV antigen-specific CD4 or CD8 T cells [10].…”

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

confidence: 99%

“…Longitudinal immunological analyses revealed that NK cells are activated and produce IFN-c prior to the increase in HBV antigen-specific CD4 or CD8 T cells [10]. IFN-c, TNF-a, and IFN-a have been reported to be key players in the mediation of non-cytopathic HBV eradication [5,[11][12][13].…”

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

confidence: 99%

“…Of particular importance, HCV-specific CD8 ? T cell response is restored in vitro in the presence of masking antibodies against PD ligand 1 (PD-L1), suggesting that the PD-1/PD-L1 pathway could serve as a therapeutic target [10,101]. In a pilot study on chimpanzees aimed at verifying the efficacy of the blockade of PD-1 using anti-PD-1 antibody against HCV infection, in one of three chimpanzees, the level of HCV-RNA was reduced during the administration of anti-PD-1 antibody, but relapsed after the cessation of treatment.…”

Section: T Cell Responses In Chronic Hcv Infectionmentioning

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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Immunity against Hepatitis B Virus and HBV Vaccines

Doi

Morikawa

Kanto

2018

Encyclopedia of Life Sciences

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Hepatitis B virus (HBV) remains a global health problem, with 257 million carriers in 2015. Birth‐dose administration of hepatitis B vaccine (HB vaccine) has significantly reduced the numbers of HBV carriers in high‐endemic countries. The clinical course of infection is dependent on viral and host factors. It is known from patients with acute hepatitis that vigorous innate and adaptive immunity is needed to clear HBV. However, HBV employs covalently closed circular DNA – a mini chromosome in the nucleus – as a replicative template that helps the virus to hide under the radar of the host immunosurveillance system, and once HBV escapes from immune clearance, pervasive impairment of various immune cells is observed in chronically infected patients. In such circumstances, complete HBV eradication is rarely attainable despite lifelong treatment with nucleos(t)ide analogues. Functional cure, the state of HB surface antigen loss, is a surrogate clinical target for patients at risk of progression to cirrhosis and hepatocellular carcinoma. Appropriate induction of both innate and adaptive immunity is vital to achieve a functional cure. Understanding the immune reaction against HBV and its impact on the clinical course of acute and chronic hepatitis, along with recent advances in HB vaccination, is key to combating this infection. Key Concepts HBV infection is a worldwide health problem that causes potentially life‐threatening liver diseases, such as liver cirrhosis and hepatocellular carcinoma. HBV cccDNA exists as a mini chromosome in the nucleus of infected hepatocytes and works as a replicative template for the production of progeny virus or HBV‐related proteins. The outcomes of primary HBV infection are influenced by the age of the host at the time of exposure. Adult patients with acute HBV infection eradicate HBV by robust activation of innate and adaptive immune reactions. Chronic HBV infection impairs the function of various immune cells, leading to the difficulty of HBV elimination. Implementation of HB vaccine in endemic countries has contributed significantly to the reduction of HBsAg‐positive carriers in the world.

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Early kinetics of innate and adaptive immune responses during hepatitis B virus infection

Abstract: The innate immune system is able to sense HBV infection, as shown by the early development of NK and NT cell responses, which probably contribute to contain the HBV infection and to allow timely induction of adaptive responses.

Cited by 259 publications

References 32 publications

Mechanism of inhibiting type I interferon induction by hepatitis B virus X protein

Mechanism of inhibiting type I interferon induction by hepatitis B virus X protein

Host–virus interactions in hepatitis B and hepatitis C infection

Immunity against Hepatitis B Virus and HBV Vaccines

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