Expression of pattern recognition receptors in liver biopsy specimens of children chronically infected with HBV and HCV

Mozer‐Lisewska, Iwona; Kowala‐Piaskowska, Arleta; Mania, Anna; Jenek, Renata; Samara, Husam; Kaczmarek, Elżbieta; Sikora, Jan; Służewski, Wojciech; Zeromski, J

doi:10.5603/fhc.2011.0058

Cited by 8 publications

(8 citation statements)

References 19 publications

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“…Importantly, NOD1 expression is augmented in hepatocytes of hepatitis C virus patients (68). We now report that, in addition to the acute response to a synthetic ligand and to ectopic expression of the viral polymerase, long-term expression of low levels of all viral proteins in mouse hepatocytes as well as bona fide infection of primary human hepatocytes with HCV also induce NOD1 expression.…”

Section: Discussionmentioning

confidence: 81%

NOD1 Participates in the Innate Immune Response Triggered by Hepatitis C Virus Polymerase

Vegna

Grégoire

Moreau

et al. 2016

J Virol

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Hepatitis C virus (HCV) triggers innate immunity signaling in the infected cell. Replication of the viral genome is dispensable for this phenotype, and we along with others have recently shown that NS5B, the viral RNA-dependent RNA polymerase, synthesizes double-stranded RNA (dsRNA) from cellular templates, thus eliciting an inflammatory response, notably via activation of type I interferon and lymphotoxin ␤. Here, we investigated intracellular signal transduction pathways involved in this process. Using HepaRG cells, a model that largely recapitulates the in vivo complexities of the innate immunity receptor signaling, we have confirmed that NS5B triggered increased expression of the canonical pattern recognition receptors (PRRs) specific for dsRNA, namely, RIG-I, MDA5, and Toll-like receptor 3 (TLR3). Unexpectedly, intracellular dsRNA also led to accumulation of NOD1, a receptor classically involved in recognition of bacterial peptidoglycans. NOD1 activation, confirmed by analysis of its downstream targets, was likely due to its interaction with dsRNA and was independent of RIG-I and mitochondrial antiviral signaling protein (MAVS/IPS-1/Cardif/VISA) signaling. It is likely to have a functional significance in the cellular response in the context of HCV infection since interference with the NOD1 pathway severely reduced the inflammatory response elicited by NS5B. IMPORTANCEIn this study, we show that NOD1, a PRR that normally senses bacterial peptidoglycans, is activated by HCV viral polymerase, probably through an interaction with dsRNA, suggesting that NOD1 acts as an RNA ligand recognition receptor. In consequence, interference with NOD1-mediated signaling significantly weakens the inflammatory response to dsRNA. These results add a new level of complexity to the understanding of the cross talk between different classes of pattern recognition receptors and may be related to certain complications of chronic hepatitis C virus infection.

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Section: Discussionmentioning

confidence: 81%

NOD1 Participates in the Innate Immune Response Triggered by Hepatitis C Virus Polymerase

Vegna

Grégoire

Moreau

et al. 2016

J Virol

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“…Expressions of TLRs are found to be increased in severe HBV infections and in cases of cirrhosis (5,12,13,16,30). It is a common finding in the literature that TLR-2 expression significantly increases in HBeAg (-) CHB patients, meanwhile inconsistent results are reported regarding TLR-4 expression (3,9,15,18,21,24,29).…”

mentioning

confidence: 70%

“…The pathogenesis and clinical manifestations of hepatitis B are due to the interaction of the virus and the host immune system. The in vitro and in vivo studies to date show that TLRs can play an important role in the pathogenesis of HBV (9,11,(13)(14)(15)(16)18,20,23,(27)(28)(29)(30). Increased expression of TLR-2 in peripheral blood monocytes and liver biopsy specimens with CHB patients has been shown (14,18,21,24,26,31,32).…”

Section: Discussionmentioning

confidence: 99%

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Serum Toll-Like Receptor-2, Toll-Like Receptor-4 Levels in Patients with HBeAg-Negative Chronic Viral Hepatitis B

et al. 2017

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Toll-like receptors (TLRs) may play an important role in hepatitis-B pathogenesis. However, serum TLR-2 and TLR-4 levels and their association with serum liver enzymes, hepatitis B virus (HBV) DNA, quantitative HBsAg levels, and liver biopsy findings, are unknown. A total of naive 40 HBeAg (-) chronic hepatitis B (CHB) patients and 20 healthy control subjects were recruited in this study. Liver tests, HBV DNA, serum TLR-2 and TLR-4, and quantitative HBsAg levels were evaluated among all groups. The relationship among TLR-2, TLR-4, quantitative HBsAg levels and liver tests, and liver histological findings were investigated with correlation analysis. Serum TLR-2 and TLR-4 levels in HBeAg (-) CHB patients were higher than in the control group. There was a positive correlation between serum TLR-2, TLR-4, and HBV DNA and ALT levels. We have further demonstrated that serum TLR-2 levels are correlated with AST and quantitative HBsAg levels. However, TLRs levels were not linked to the liver biopsy findings. TLR can have an important role in hepatitis B pathogenesis. Liver injury in CHB may cause elevated TLR-2 and TLR-4 levels.

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“…Finally, although human biopsies provide limited opportunities for mechanistic studies, they are critical since they allow a snapshot view of the tissue that is infected in the actual host. Consistent with this concept, Mozer-Lisewska et al reported that in liver from patients with chronic hepatitis C infection, the expression of TLR1, 2, 4, NALP, and RIG-I helicase was markedly increased, suggesting that these PRRs may be important for the pathogenesis of chronic viral hepatitis by HCV in humans (41). …”

Section: Hepatitis C Virusmentioning

confidence: 85%

Recognition of Human Oncogenic Viruses by Host Pattern-Recognition Receptors

Paolo

2014

Front. Immunol.

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Human oncogenic viruses include Epstein–Barr virus, hepatitis B virus, hepatitis C virus, human papilloma virus, human T-cell lymphotropic virus, Kaposi’s associated sarcoma virus, and Merkel cell polyomavirus. It would be expected that during virus–host interaction, the immune system would recognize these pathogens and eliminate them. However, through evolution, these viruses have developed a number of strategies to avoid such an outcome and successfully establish chronic infections. The persistent nature of the infection caused by these viruses is associated with their oncogenic potential. In this article, we will review the latest information on the interaction between oncogenic viruses and the innate immune system of the host. In particular, we will summarize the available knowledge on the recognition by host pattern-recognition receptors of pathogen-associated molecular patterns present in the incoming viral particle or generated during the virus’ life cycle. We will also review the data on the recognition of cell-derived danger associated molecular patterns generated during the virus infection that may impact the outcome of the host–pathogen interaction and the development cancer.

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Expression of pattern recognition receptors in liver biopsy specimens of children chronically infected with HBV and HCV

Cited by 8 publications

References 19 publications

NOD1 Participates in the Innate Immune Response Triggered by Hepatitis C Virus Polymerase

NOD1 Participates in the Innate Immune Response Triggered by Hepatitis C Virus Polymerase

Serum Toll-Like Receptor-2, Toll-Like Receptor-4 Levels in Patients with HBeAg-Negative Chronic Viral Hepatitis B

Recognition of Human Oncogenic Viruses by Host Pattern-Recognition Receptors

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