Activation of Type I and Type III Interferons in Chronic Hepatitis C

Mihm, Sabine

doi:10.1159/000369973

Cited by 18 publications

(18 citation statements)

References 64 publications

(90 reference statements)

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“…Studies on the impact of IFN-λs in clinical scenarios have been dominated by the strong association of IFNL3/L4 SNPs with spontaneous clearance of HCV and IFN-α treatment response (79,80,87,90,103,111). Details on this important association have been reviewed in detail elsewhere (165)(166)(167). The association between IFN-λ SNPs and other infectious diseases is far less well explored.…”

Section: Borrelia Burgdorferimentioning

confidence: 99%

Interferon Lambda: Modulating Immunity in Infectious Diseases

2017

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Interferon lambdas (IFN-λs; IFNL1-4) modulate immunity in the context of infections and autoimmune diseases, through a network of induced genes. IFN-λs act by binding to the heterodimeric IFN-λ receptor (IFNLR), activating a STAT phosphorylation-dependent signaling cascade. Thereby hundreds of IFN-stimulated genes are induced, which modulate various immune functions via complex forward and feedback loops. When compared to the well-characterized IFN-α signaling cascade, three important differences have been discovered. First, the IFNLR is not ubiquitously expressed: in particular, immune cells show significant variation in the expression levels of and susceptibilities to IFN-λs. Second, the binding affinities of individual IFN-λs to the IFNLR varies greatly and are generally lower compared to the binding affinities of IFN-α to its receptor. Finally, genetic variation in the form of a series of single-nucleotide polymorphisms (SNPs) linked to genes involved in the IFN-λ signaling cascade has been described and associated with the clinical course and treatment outcomes of hepatitis B and C virus infection. The clinical impact of IFN-λ signaling and the SNP variations may, however, reach far beyond viral hepatitis. Recent publications show important roles for IFN-λs in a broad range of viral infections such as human T-cell leukemia type-1 virus, rotaviruses, and influenza virus. IFN-λ also potentially modulates the course of bacterial colonization and infections as shown for Staphylococcus aureus and Mycobacterium tuberculosis. Although the immunological processes involved in controlling viral and bacterial infections are distinct, IFN-λs may interfere at various levels: as an innate immune cytokine with direct antiviral effects; or as a modulator of IFN-α-induced signaling via the suppressor of cytokine signaling 1 and the ubiquitin-specific peptidase 18 inhibitory feedback loops. In addition, the modulation of adaptive immune functions via macrophage and dendritic cell polarization, and subsequent priming, activation, and proliferation of pathogen-specific T- and B-cells may also be important elements associated with infectious disease outcomes. This review summarizes the emerging details of the IFN-λ immunobiology in the context of the host immune response and viral and bacterial infections.

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Section: Borrelia Burgdorferimentioning

confidence: 99%

Interferon Lambda: Modulating Immunity in Infectious Diseases

2017

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“…Chronic hepatitis C (CHC) infected individuals have mild liver inflammation (Figure 6C ), stable HCV RNA titers, and liver disease that progresses especially in the presence of other risk factors (age, male, obesity, diabetes alcohol, HIV or HBV co-infection)[ 76 ]. HCV infection activates intrinsic type I and III IFN responses which induces transcription of innate-antiviral IFN stimulated genes[ 77 ]. Adaptive viral-specific CD8+/CD4+ T-cells and natural killer cells facilitate the release of pro-inflammatory cytokines and growth factors while destroying of HCV infected hepatocytes by promoting the inflammation-necrosis-proliferation cycle[ 78 ].…”

Section: Chronic Inflammation-mediated By Viral Hepatitismentioning

confidence: 99%

Molecular mechanisms of viral hepatitis induced hepatocellular carcinoma

D’souza

Lau

Coffin

et al. 2020

WJG

170

127

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Chronic infection with viral hepatitis affects half a billion individuals worldwide and can lead to cirrhosis, cancer, and liver failure. Liver cancer is the third leading cause of cancer-associated mortality, of which hepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. Solid tumors like HCC are complex and have heterogeneous tumor genomic profiles contributing to complexity in diagnosis and management. Chronic infection with hepatitis B virus (HBV), hepatitis delta virus (HDV), and hepatitis C virus (HCV) are the greatest etiological risk factors for HCC. Due to the significant role of chronic viral infection in HCC development, it is important to investigate direct (viral associated) and indirect (immune-associated) mechanisms involved in the pathogenesis of HCC. Common mechanisms used by HBV, HCV, and HDV that drive hepatocarcinogenesis include persistent liver inflammation with an impaired antiviral immune response, immune and viral protein-mediated oxidative stress, and deregulation of cellular signaling pathways by viral proteins. DNA integration to promote genome instability is a feature of HBV infection, and metabolic reprogramming leading to steatosis is driven by HCV infection. The current review aims to provide a brief overview of HBV, HCV and HDV molecular biology, and highlight specific viral-associated oncogenic mechanisms and common molecular pathways deregulated in HCC, and current as well as emerging treatments for HCC.

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“…DOI: 10.1159/000508076 the host's capability to encode a functional IFN-λ 4 protein [8]. Paradoxically, the IFNL4 knockout variant TT is favorable for virus eradication and resolution of infection, presumably by the deactivation of an IFN-αdesensitizing control mechanism, antagonizing IFN-α efficacy [9].…”

Section: Dear Editormentioning

confidence: 99%

Activation of Type I and Type III Interferons in Chronic Hepatitis C

Cited by 18 publications

References 64 publications

Interferon Lambda: Modulating Immunity in Infectious Diseases

Interferon Lambda: Modulating Immunity in Infectious Diseases

Molecular mechanisms of viral hepatitis induced hepatocellular carcinoma

COVID-19: Possible Impact of the Genetic Background in <b><i>IFNL</i></b> Genes on Disease Outcomes

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