scholarly journals Hepatitis C virus - T-cell responses and viral escape mutations

2011 ◽  
Vol 42 (1) ◽  
pp. 17-26 ◽  
Author(s):  
Danijela Petrovic ◽  
Eugene Dempsey ◽  
Derek G. Doherty ◽  
Dermot Kelleher ◽  
Aideen Long
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
T Cell Responses ◽  
Viral Escape ◽  
Cell Responses

scholarly journals Cellular immune selection with hepatitis C virus persistence in humans

2005 ◽  
Vol 201 (11) ◽  
pp. 1741-1752 ◽  
Author(s):  
Andrea L. Cox ◽  
Timothy Mosbruger ◽  
Qing Mao ◽  
Zhi Liu ◽  
Xiao-Hong Wang ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Viral Escape ◽  
Sequence Evolution ◽  
T Cell Epitopes ◽  
Cell Responses ◽  
Cellular Immune

Hepatitis C virus (HCV) infection frequently persists despite substantial virus-specific cellular immune responses. To determine if immunologically driven sequence variation occurs with HCV persistence, we coordinately analyzed sequence evolution and CD8+ T cell responses to epitopes covering the entire HCV polyprotein in subjects who were followed prospectively from before infection to beyond the first year. There were no substitutions in T cell epitopes for a year after infection in a subject who cleared viremia. In contrast, in subjects with persistent viremia and detectable T cell responses, we observed substitutions in 69% of T cell epitopes, and every subject had a substitution in at least one epitope. In addition, amino acid substitutions occurred 13-fold more often within than outside T cell epitopes (P < 0.001, range 5–38). T lymphocyte recognition of 8 of 10 mutant peptides was markedly reduced compared with the initial sequence, indicating viral escape. Of 16 nonenvelope substitutions that occurred outside of known T cell epitopes, 8 represented conversion to consensus (P = 0.015). These findings reveal two distinct mechanisms of sequence evolution involved in HCV persistence: viral escape from CD8+ T cell responses and optimization of replicative capacity.

scholarly journals Absence of viral escape within a frequently recognized HLA-A26-restricted CD8+ T-cell epitope targeting the functionally constrained hepatitis C virus NS5A/5B cleavage site

2007 ◽  
Vol 88 (7) ◽  
pp. 1986-1991 ◽  
Author(s):  
Christoph Neumann-Haefelin ◽  
Thomas Killinger ◽  
Jörg Timm ◽  
Scott Southwood ◽  
Denise McKinney ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Cleavage Site ◽  
Cell Epitope ◽  
T Cell Responses ◽  
Hcv Infection ◽  
Viral Fitness ◽  
Viral Escape ◽  
Cell Responses

CD8+ T-cell responses are central for the resolution of hepatitis C virus (HCV) infection, and viral escape from these CD8+ T-cell responses has been suggested to play a major role in HCV persistence. However, the factors determining the emergence of CD8 escape mutations are not well understood. Here, the first identification of four HLA-A26-restricted CD8+ T-cell epitopes is reported. Of note, two of these four epitopes are located in the NS3/4A and NS5A/5B cleavage sites. The latter epitope is targeted in all (three of three) patients with acute, resolving HCV infection and in a relatively high proportion (four of 14) of patients with chronic HCV infection. Importantly, the epitope corresponding to the NS5A/5B cleavage site is characterized by the complete absence of sequence variations, despite the presence of functional virus-specific CD8+ T cells in our cohort. These results support previous findings that showed defined functional constraints within this region. They also suggest that the absence of viral escape may be determined by viral fitness cost and highlight an attractive target for immunotherapies.

scholarly journals Optimising T cell (re)boosting strategies for adenoviral and modified vaccinia Ankara vaccine regimens in humans

npj Vaccines ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Stefania Capone ◽  
Anthony Brown ◽  
Felicity Hartnell ◽  
Mariarosaria Del Sorbo ◽  
Cinzia Traboni ◽  
...  
Keyword(s):  
T Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Viral Vectors ◽  
Standard Dose ◽  
T Cell Responses ◽  
Effector Memory ◽  
Cell Responses ◽  
Wide Range

Abstract Simian adenoviral and modified vaccinia Ankara (MVA) viral vectors used in heterologous prime-boost strategies are potent inducers of T cells against encoded antigens and are in advanced testing as vaccine carriers for a wide range of infectious agents and cancers. It is unclear if these responses can be further enhanced or sustained with reboosting strategies. Furthermore, despite the challenges involved in MVA manufacture dose de-escalation has not been performed in humans. In this study, healthy volunteers received chimpanzee-derived adenovirus-3 and MVA vaccines encoding the non-structural region of hepatitis C virus (ChAd3-NSmut/MVA-NSmut) 8 weeks apart. Volunteers were then reboosted with a second round of ChAd3-NSmut/MVA-NSmut or MVA-NSmut vaccines 8 weeks or 1-year later. We also determined the capacity of reduced doses of MVA-NSmut to boost ChAd3-NSmut primed T cells. Reboosting was safe, with no enhanced reactogenicity. Reboosting after an 8-week interval led to minimal re-expansion of transgene-specific T cells. However, after a longer interval, T cell responses expanded efficiently and memory responses were enhanced. The 8-week interval regimen induced a higher percentage of terminally differentiated and effector memory T cells. Reboosting with MVA-NSmut alone was as effective as with ChAd3-NSmut/MVA-NSmut. A ten-fold lower dose of MVA (2 × 107pfu) induced high-magnitude, sustained, broad, and functional Hepatitis C virus (HCV)-specific T cell responses, equivalent to standard doses (2 × 108 pfu). Overall, we show that following Ad/MVA prime-boost vaccination reboosting is most effective after a prolonged interval and is productive with MVA alone. Importantly, we also show that a ten-fold lower dose of MVA is as potent in humans as the standard dose.

PS-030-Cure of hepatitis C virus has limited impact on the functional and mitochondrial impairment of HCV-specific CD8+ T-cell responses

2019 ◽  
Vol 70 (1) ◽  
pp. e22
Author(s):  
Amare Aregay ◽  
Solomon Owusu Sekyere ◽  
Katja Deterdig ◽  
Kerstin Port ◽  
Julia Dietz ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Limited Impact ◽  
Cell Responses ◽  
Mitochondrial Impairment

scholarly journals Impaired Hepatitis C Virus-Specific T Cell Responses and Recurrent Hepatitis C Virus in HIV Coinfection

PLoS Medicine ◽  
2006 ◽  
Vol 3 (12) ◽  
pp. e492 ◽  
Author(s):  
Arthur Y Kim ◽  
Julian Schulze zur Wiesch ◽  
Thomas Kuntzen ◽  
Joerg Timm ◽  
Daniel E Kaufmann ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
T Cell Responses ◽  
Recurrent Hepatitis ◽  
Cell Responses ◽  
Hiv Coinfection ◽  
Recurrent Hepatitis C

scholarly journals The Hepatitis C Virus Core Protein Modulates T Cell Responses by Inducing Spontaneous and Altering T-cell Receptor-triggered Ca2+Oscillations

2003 ◽  
Vol 278 (21) ◽  
pp. 18877-18883 ◽  
Author(s):  
Anders Bergqvist ◽  
Sara Sundström ◽  
Lina Y. Dimberg ◽  
Erik Gylfe ◽  
Maria G. Masucci
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
T Cell Receptor ◽  
Core Protein ◽  
T Cell Responses ◽  
Cell Receptor ◽  
Cell Responses ◽  
Virus Core

scholarly journals Spontaneous clearance of chronic hepatitis C after liver transplantation: Are hepatitis C virus-specific T cell responses the clue?

2008 ◽  
Vol 14 (8) ◽  
pp. 1225-1227 ◽  
Author(s):  
P. V. Suneetha ◽  
Ingmar Mederacke ◽  
Albert Heim ◽  
Murat Bastürk ◽  
Markus Cornberg ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Chronic Hepatitis C ◽  
T Cell Responses ◽  
Spontaneous Clearance ◽  
Cell Responses
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