Journal ArticleDOI
Evasion of intracellular host defence by hepatitis C virus
Michael Gale,Eileen Foy +1 more
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TLDR
Hepatitis C virus evades the host response through a complex combination of processes that include signalling interference, effector modulation and continual viral genetic variation.Abstract:
Viral infection of mammalian cells rapidly triggers intracellular signalling events leading to interferon alpha/beta production and a cellular antiviral state. This 'host response' is our first line of immune defence against infection as it imposes several barriers to viral replication and spread. Hepatitis C virus (HCV) evades the host response through a complex combination of processes that include signalling interference, effector modulation and continual viral genetic variation. These evasion strategies support persistent infection and the spread of HCV. Defining the molecular mechanisms by which HCV regulates the host response is of crucial importance and may reveal targets for novel therapeutic strategies.read more
Citations
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Journal ArticleDOI
Hepatocellular carcinoma pathogenesis: from genes to environment
TL;DR: The current state of knowledge of hepatitis C, the most common and dreaded liver neoplasm, is summarized, and the principal challenges and scientific opportunities that are relevant to controlling this accelerating global health crisis are highlighted.
Journal ArticleDOI
Vaccine Adjuvants: Putting Innate Immunity to Work
TL;DR: There remains a need for improved adjuvants that enhance protective antibody responses, especially in populations that respond poorly to current vaccines, and the larger challenge is to develop vaccines that generate strong T cell immunity with purified or recombinant vaccine antigens.
Journal ArticleDOI
Innate immunity induced by composition-dependent RIG-I recognition of hepatitis C virus RNA
TL;DR: This work identifies the polyuridine motif of the HCV genome 3′ non-translated region and its replication intermediate as the PAMP substrate of RIG-I, and shows that this and similar homopolyuridine or homopolyriboadenine motifs present in the genomes of RNA viruses are the chief feature of Rig-I recognition and immune triggering in human and murine cells.
Journal ArticleDOI
The interferon response circuit: Induction and suppression by pathogenic viruses
TL;DR: The current view on the balancing act between virus-induced IFN responses and the viral counterplayers is discussed.
Journal ArticleDOI
Interferon signaling and treatment outcome in chronic hepatitis C
Magdalena Sarasin-Filipowicz,Edward J. Oakeley,Francois H.T. Duong,Verena Christen,Luigi Terracciano,Witold Filipowicz,Markus H. Heim +6 more
TL;DR: The concept that activation of the endogenous IFN system in CHC not only is ineffective in clearing the infection but also may impede the response to therapy, most likely by inducing a refractory state of the IFN signaling pathway, is supported.
References
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Journal ArticleDOI
Toll-like receptor control of the adaptive immune responses.
Akiko Iwasaki,Ruslan Medzhitov +1 more
TL;DR: Recognition of microbial infection and initiation of host defense responses is controlled by multiple mechanisms and recent studies have provided important clues about the mechanisms of TLR-mediated control of adaptive immunity orchestrated by dendritic cell populations in distinct anatomical locations.
Journal ArticleDOI
The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses.
Mitsutoshi Yoneyama,Mika Kikuchi,Takashi Natsukawa,Noriaki Shinobu,Tadaatsu Imaizumi,Makoto Miyagishi,Kazunari Taira,Shizuo Akira,Takashi Fujita +8 more
TL;DR: In this article, the authors identify retinoic acid inducible gene I (RIG-I), which encodes a DExD/H box RNA helicase that contains a caspase recruitment domain, as an essential regulator for dsRNA-induced signaling.
Journal ArticleDOI
Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway.
Masahiro Yamamoto,Shintaro Sato,Hiroaki Hemmi,Katsuaki Hoshino,Tsuneyasu Kaisho,Hideki Sanjo,Osamu Takeuchi,Masanaka Sugiyama,Masaru Okabe,Kiyoshi Takeda,Shizuo Akira +10 more
TL;DR: It is shown that TRIF is essential for TLR3- and TLR4-mediated signaling pathways facilitating mammalian antiviral host defense and complete loss of nuclear factor kappa B activation in response toTLR4 stimulation is demonstrated.
Journal ArticleDOI
Production of infectious hepatitis C virus in tissue culture from a cloned viral genome
Takaji Wakita,Thomas Pietschmann,Takanobu Kato,Takanobu Kato,Tomoko Date,Michiko Miyamoto,Zijiang Zhao,Krishna K. Murthy,Anja Habermann,Hans-Georg Kräusslich,Masashi Mizokami,Ralf Bartenschlager,T. Jake Liang +12 more
TL;DR: It is shown that the JFH1 genome replicates efficiently and supports secretion of viral particles after transfection into a human hepatoma cell line (Huh7) and provides a powerful tool for studying the viral life cycle and developing antiviral strategies.
Journal ArticleDOI
IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway.
Katherine A. Fitzgerald,Sarah M. McWhirter,Kerrie L. Faia,Daniel C. Rowe,Eicke Latz,Douglas T. Golenbock,Anthony J. Coyle,Sha-Mei Liao,Tom Maniatis +8 more
TL;DR: It is reported that the noncanonical IκB kinase homologs, IKKε (IKKε) and TANK-binding kinase-1 (TBK1), which were previously implicated in NF-κB activation, are also essential components of the IRF3 signaling pathway.
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