Abstract
Annual Review of Immunology
Vol. 25:
71-99
(Volume publication date April 2007)
(doi:10.1146/annurev.immunol.25.022106.141602)
First published online as a Review in Advance on October 26, 2006Flying Under the Radar: The Immunobiology of Hepatitis C Lynn B. Dustin and Charles M. RiceThe Rockefeller University, Center for the Study of Hepatitis C, New York, NY 10021; email: dustinl@rockefeller.edu Abstract The hepatitis C virus (HCV) is a remarkably successful pathogen, establishing persistent infection in more than two-thirds of those who contract it. Its success is related to its abilities to blunt innate antiviral pathways and to evade adaptive immune responses. These two themes may be related. We propose that HCV takes advantage of the impaired innate response to delay the organization of an effective adaptive immune attack. The tolerogenic liver environment may provide cover, prolonging this delay. HCV's error-prone replication strategy permits rapid evolution under immune pressure. Persistent high levels of viral antigens may contribute to immune exhaustion. Finally, the virus may benefit from the efficient enlistment of memory T and B cells in the pursuit of a moving target. Acronyms and Definitions Cryoglobulins: abnormal immunoglobulins that precipitate reversibly at low temperatures (<37°C). Type II cryoglobulins are composed of a monoclonal IgM, often rheumatoid factor, complexed with polyclonal IgG DC: dendritic cell Double-stranded RNA (dsRNA): a pathogen-associated molecular pattern. dsRNA is produced during infection by HCV, as for most viruses. The HCV genome also has an extensive secondary structure that may be recognized as dsRNA and activate antiviral pathways GP: glycoprotein HCV: hepatitis C virus HCV pseudoparticle (HCVpp): a surrogate system for studying HCV entry. HCVpp binds and enters target cells in a manner dependent on the E1 and E2 GPs and delivers reporters such as luciferase or green fluorescent protein that can be used to quantify infection HCV replicon: transfected RNA that persists and replicates autonomously in a cell line, without undergoing an infectious cycle HLA: human leukocyte antigen ISG: IFN-stimulated gene LSEC: liver sinusoidal endothelial cell MC: mixed cryoglobulinemia nAb: neutralizing antibody Most recent citing papers (via CrossRef)PD-L1 negatively regulates CD4+CD25+Foxp3+ Tregs by limiting STAT-5 phosphorylation in patients chronically infected with HCV Journal of Clinical Investigation 119(3):551-564 (2009) Chemokines in the immunopathogenesis of hepatitis C infection Hepatology 49(2):676-688 (2009) Characterization of the cellular immune response in hepatitis C virus infection Medicinal Research Reviews:n/a-n/a (2009) Natural killer cell function is intact after direct exposure to infectious hepatitis C virions Hepatology 49(1):12-21 (2009) Genome-wide hepatitis C virus amino acid covariance networks can predict response to antiviral therapy in humans Journal of Clinical Investigation (2009)
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