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Emerging concepts in immunity to hepatitis C virus infection
Hugo R. Rosen
Hugo R. Rosen
Published October 1, 2013
Citation Information: J Clin Invest. 2013;123(10):4121-4130. https://doi.org/10.1172/JCI67714.
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Review

Emerging concepts in immunity to hepatitis C virus infection

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Abstract

Since the discovery of hepatitis C virus (HCV) by molecular cloning almost a quarter of a century ago, unprecedented at the time because the virus had never been grown in cell culture or detected serologically, there have been impressive strides in many facets of our understanding of the natural history of the disease, the viral life cycle, the pathogenesis, and antiviral therapy. It is apparent that the virus has developed multiple strategies to evade immune surveillance and eradication. This Review covers what we currently understand of the temporal and spatial immunological changes within the human innate and adaptive host immune responses that ultimately determine the outcomes of HCV infection.

Authors

Hugo R. Rosen

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Figure 3

Interplay of host T cell responses and the evolution of HCV epitopes.

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Interplay of host T cell responses and the evolution of HCV epitopes.
(A...
(A) A sustained CD4+ T cell response with multispecific CTLs may constrain the development of viral escape mutations, leading to viral clearance during acute infection. (B) If CTL responses are weak (manifested by high PD-1 and TIM3 expression) with impaired CD4 help and priming, escape mutations likely will not develop. High viral levels and intact HCV epitopes are associated with increased levels of inhibitory receptors. (C) Failure of the CD4+ T cell response in the presence of a narrow but vigorous CTL response favors the development of escape mutations. Additional compensatory mutations may be required for replicative fitness (120–122). Viral amino acid substitution is associated with decreased inhibitory receptor expression on CTLs, perhaps accounting for their robust proliferation to wild-type, nonmutated virus (115). (D) Without a restricting HLA allele and immune selective pressure, reversion to the wild-type sequence likely occurs because of the high fitness cost associated with an escape mutation. (Adapted with permission from The Journal of Experimental Medicine [ref. 118].)

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