Stealth and cunning: hepatitis B and hepatitis C viruses.
TLDR
The unexpected finding that HBV does not modulate host cellular gene transcription and apparently does not induce an innate immune response when spreading through the liver raises the possibility thatHBV, unlike HCV and other viruses, has evolved to evade innate immunity by not inducing it rather then actively counteracting it.Abstract:
Collectively, the results summarized in this review suggest that HBV acts like a stealth virus early in infection, remaining undetected and spreading until the onset of the adaptive immune response several weeks later. We suspect that the relative invisibility of HBV to the innate sensing machinery of the cells reflects its replication strategy, which sequesters the transcriptional template in the nucleus, entails the production of capped and polyadenylated viral mRNAs that resemble the structure of normal cellular transcripts, and the replicating viral genome is sheltered within viral capsid particles in the cytoplasm and, therefore, does not elicit a response. In contrast, HCV activates a strong intracellular antiviral response in the liver, presumably because it replicates via a dsRNA intermediate in the cytoplasm, where it can readily induce the cellular dsRNA sensing apparatus and initiate the signaling cascade. In turn, this results in the induction of many genes, such as the 2′,5′-oligoadenylate synthetase Mx1, that have known antiviral activity (reviewed in references 128 and 141); TRIM14 and 22, members of the same gene family as TRIM5, which has been shown to be part of the host defense against retroviruses (reviewed in reference 11); and ISG15, which has recently been proposed to have a role in innate immunity (124). Impressively, however, HCV cunningly manages to spread through the liver despite induction of these genes, presumably because its E2, NS3, and NS5A proteins can defeat them. On the other hand, both viruses can be controlled when CD8+ T cells enter the liver, recognize antigen, kill whatever infected cells they encounter, and secrete IFN-γ, which triggers a broad-based cascade that amplifies the inflammatory process and has antiviral activity, at least in HBV-transgenic mice and the HBV and HCV cell culture systems. The unexpected finding that HBV does not modulate host cellular gene transcription and apparently does not induce an innate immune response when spreading through the liver raises the possibility that HBV, unlike HCV and other viruses, has evolved to evade innate immunity by not inducing it rather then actively counteracting it; this, in turn, might leave HBV very sensitive to intracellular antiviral mechanisms when they are induced by the adaptive immune system or an unrelated viral infection. Although we suggest that HBV and HCV infections can be inhibited noncytopathically by the cellular genes that are induced during this process, the identities of those genes, the antiviral mechanisms they elicit, and the unique evasion strategies of each virus remain to be determined, marking a new starting point in the quest to understand the cellular and molecular immunobiology of these viral infections.read more
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Hepatitis B virus infection
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Interferon modulation of cellular microRNAs as an antiviral mechanism.
Irene M. Pedersen,Guofeng Cheng,Stefan Wieland,Stefano Volinia,Carlo M. Croce,Francis V. Chisari,Michael David +6 more
TL;DR: These findings strongly support the notion that mammalian organisms too, through the interferon system, use cellular miRNAs to combat viral infections.
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Anti-Immunology: Evasion of the Host Immune System by Bacterial and Viral Pathogens
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TL;DR: This review highlights and compares some of the many molecular mechanisms that bacterial and viral pathogens use to evade host immune defenses.
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References
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Replication of Subgenomic Hepatitis C Virus RNAs in a Hepatoma Cell Line
TL;DR: This work defines the structure of HCV replicons functional in cell culture and provides the basis for a long-sought cellular system that should allow detailed molecular studies ofHCV and the development of antiviral drugs.
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Hepatitis C Virus Infection
Georg M. Lauer,Bruce D. Walker +1 more
TL;DR: The institution of blood-screening measures in developed countries has decreased the risk of transfusion-associated hepatitis to a negligible level, but new cases continue to occur mainly as a result of injection-drug use and, to a lesser degree, through other means of percutaneous or mucous-membrane exposure.
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Antiviral Actions of Interferons
TL;DR: Tremendous progress has been made in understanding the molecular basis of the antiviral actions of interferons (IFNs), as well as strategies evolved by viruses to antagonize the actions of IFNs.