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Cellular immune selection with hepatitis C virus persistence in humans.
Andrea L Cox1, Timothy Mosbruger, Qing Mao
1Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA. acox@jhmi.edu
The Journal of Experimental Medicine
|June 9, 2005
Summary
Hepatitis C virus (HCV) persistence involves immune escape from CD8+ T cell responses, leading to viral sequence variation within T cell epitopes. This viral evolution helps the virus evade immune detection and persist in infected individuals.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Hepatitis C virus (HCV) infection often persists despite strong immune responses.
- Understanding the mechanisms of viral persistence is crucial for developing effective treatments.
Purpose of the Study:
- To investigate if immune responses drive sequence variation in HCV during persistent infection.
- To analyze the relationship between viral evolution and CD8+ T cell responses to HCV epitopes.
Main Methods:
- Prospective analysis of viral sequence evolution and CD8+ T cell responses.
- Coordinated analysis of T cell epitopes across the entire HCV polyprotein.
- Comparison of sequence variation within and outside T cell epitopes.
Main Results:
- In subjects with persistent HCV, 69% of T cell epitopes showed substitutions, with every subject having at least one.
- Amino acid substitutions occurred 13-fold more often within T cell epitopes than outside (P < 0.001).
- Mutant viral peptides showed reduced T cell recognition, indicating viral escape; some non-envelope substitutions also occurred.
Conclusions:
- HCV persistence is associated with distinct viral evolution mechanisms, including immune escape from CD8+ T cells.
- Viral sequence variation within T cell epitopes is a key factor in HCV persistence.
- HCV utilizes viral escape and optimization of replicative capacity to evade immune responses.