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Viral Hepatitis
Transmission of HBV DNA Mediated by Ceramide-Triggered Extracellular Vesicles
An extracellular vesicle (EV) is a nanovesicle that shuttles proteins, nucleic acids, and lipids, thereby influencing cell behavior. A recent crop of reports have shown that EVs are involved in infectious biology, influencing host immunity and playing a role in the viral life cycle. In the present work, we investigated the EV-mediated transmission of hepatitis B virus (HBV) infection.Increased Mitochondrial Genetic Diversity in Persons Infected With Hepatitis C Virus
The host genetic environment contributes significantly to the outcomes of hepatitis C virus (HCV) infection and therapy response, but little is known about any effects of HCV infection on the host beyond any changes related to adaptive immune responses. HCV persistence is associated strongly with mitochondrial dysfunction, with liver mitochondrial DNA (mtDNA) genetic diversity linked to disease progression.Hepatitis C Virus-Induced Monocyte Differentiation Into Polarized M2 Macrophages Promotes Stellate Cell Activation via TGF-β
Monocyte and macrophage (MΦ) activation contributes to the pathogenesis of chronic hepatitis C virus (HCV) infection. Disease pathogenesis is regulated by both liver-resident MΦs and monocytes recruited as precursors of MΦs into the damaged liver. Monocytes differentiate into M1 (classic/proinflammatory) or M2 (alternative/anti-inflammatory) polarized MΦs in response to tissue microenvironment. We hypothesized that HCV-infected hepatoma cells (infected with Japanese fulminant hepatitis-1 [Huh7.5/JFH-1]) induce monocyte differentiation into polarized MΦs.Natural Killer Cells in Viral Hepatitis
Natural killer (NK) cells are traditionally regarded as first-line effectors of the innate immune response, but they also have a distinct role in chronic infection. Here, we review the role of NK cells against hepatitis C virus (HCV) and hepatitis B virus (HBV), two agents that cause acute and chronic hepatitis in humans. Interest in NK cells was initially sparked by genetic studies that demonstrated an association between NK cell–related genes and the outcome of HCV infection. Viral hepatitis also provides a model to study the NK cell response to both endogenous and exogenous type I interferon (IFN).Angiogenesis and Fibrogenesis in Chronic Liver Diseases
Pathologic angiogenesis appears to be intrinsically associated with the fibrogenic progression of chronic liver diseases, which eventually leads to the development of cirrhosis and related complications, including hepatocellular carcinoma. Several laboratories have suggested that this association is relevant for chronic liver disease progression, with angiogenesis proposed to sustain fibrogenesis. This minireview offers a synthesis of relevant findings and opinions that have emerged in the last few years relating liver angiogenesis to fibrogenesis.Novel Biomarkers Associated With the Outcome of Interferon-Based Hepatitis C Virus Therapy
The past 25 years since the discovery of hepatitis C virus (HCV) have been marked by significant advances in both understanding the biology of the virus and its interactions with the human host as well as developing treatment strategies that now allow a majority of patients to be cured. Combination therapy consisting of pegylated interferon-α (IFNα) 2a/2b and ribavirin was the standard of care for treating hepatitis C for almost a decade until the approval of first generation NS3/4A protease inhibitors in 2011.Does Massive Antigen Burden Allow Hepatic Viruses to Induce Regulatory T Cells and Their Tolerance and Persistence?
Regulatory T cells (Tregs), typically expressing CD25 and the transcription factor forkhead box P3 (FoxP3)—which suppress effector T-cells via contact-dependent mechanisms and immunosuppressive cytokines such as interleukin 10 (IL-10) and transforming growth factor β (TGFβ)—play a critical role in the establishment of chronic hepatitis infections in humans.1 Although primate studies have contributed significantly to our understanding of innate and adaptive responses, and have shown that Tregs are induced in both resolving and persistent viral hepatitis infection, understanding the mechanisms by which Tregs are themselves induced and then induce tolerance in vivo has been hampered by the absence of a convenient and authentic small-animal model of these infections.Oxidized Low-Density Lipoprotein Is a Novel Predictor of Interferon Responsiveness in Chronic Hepatitis C Infection
Hepatitis C virus (HCV) cell entry is mediated by several cell surface receptors, including scavenger receptor class B type I (SR-BI). Oxidized low density lipoprotein (oxLDL) inhibits the interaction between HCV and SR-BI in a noncompetitive manner. We tested whether serum oxLDL levels correlate with sustained virologic response (SVR) rates after interferon-based treatment of chronic hepatitis C.Expression of Viral Antigen by the Liver Leads to Chronic Infection Through the Generation of Regulatory T Cells
The constant exposure of the liver to food and bacterial antigens through the mesenteric circulation requires it to maintain tolerance while preserving the ability to mount an effective immune response against pathogens. We investigated the contribution of the liver’s tolerogenic nature on the establishment of chronic viral infections.
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