Abstract
The hepatitis C virus is unique among chronic viral infections in that an acute outcome with complete viral elimination is observed in a minority of infected patients. This unique feature allows direct comparison of successful immune responses with those that fail in the setting of the same human infection. Here we review how this scenario can be used to achieve better understanding of transcriptional regulation of T-cell differentiation. Specifically, we discuss results from a study comparing transcriptional profiles of hepatitis C virus (HCV)-specific CD8 T-cells during early HCV infection between patients that do and do not control and eliminate HCV. Identification of early gene expression differences in key T-cell differentiation molecules as well as clearly distinct transcriptional networks related to cell metabolism and nucleosomal regulation reveal novel insights into the development of exhausted and memory T-cells. With additional transcriptional studies of HCV-specific CD4 and CD8 T-cells in different stages of infection currently underway, we expect HCV infection to become a valuable model disease to study human immunity to viruses.
Highlights
Infection with hepatitis C virus (HCV) is unique among chronic viral infections in humans because a significant proportion of newly infected persons (~20%–30%) can completely eliminate the virus, typically within six months of exposure [1]
Based on the interest in determining correlates of both protective and failing immunity and the observation that HCV-specific CD8 T-cells are detectable in most patients during the initial 6 months of infection at relatively high frequencies, we focused our first direct ex-vivo transcriptional analysis on CD8 T-cells during early HCV infection
We reviewed the first study utilizing HCV infection as a unique model disease for in-depth analysis of transcriptional regulation in human virus-specific T cells associated with distinct infection outcomes
Summary
Infection with hepatitis C virus (HCV) is unique among chronic viral infections in humans because a significant proportion of newly infected persons (~20%–30%) can completely eliminate the virus, typically within six months of exposure [1] This observation supports the prospect of an HCV vaccine that can at least prevent chronicity and its harmful sequelae, such as end-stage liver disease and cancer, if sterilizing immunity is not feasible. As the only chronic viral infection in both humans and animals that can be cured through a highly specific targeted small molecule intervention, we can study the effects of removing the root cause of immune exhaustion (i.e., chronic antigenic stimulation) from the host-pathogen interaction Despite these unique opportunities for basic investigations into human immunology, our knowledge base regarding molecular regulation of successful and failing immunity against HCV remains limited. HCV infection could be a model human disease to understand key differences between protective and failing immunity
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
