Work

Priming of Antiviral CD8 T Cells without Effector Function by a Persistently Replicating Hepatitis C-Like Virus

Year: 2020

Type: article

Abstract: Development of vaccines against hepatitis C virus (HCV), a major cause of cirrhosis and cancer, has been stymied by a lack of animal models. The recent discovery of an HCV-like rodent hepacivirus (RHV) enabled the development of such a model in rats. This platform recapitulates HCV hepatotropism and viral chronicity necessary for vaccine testing. Currently, there are few descriptions of RHV-specific responses and why they fail to prevent persistent infection in this model. Here, we show that RHV-specific CD8 T cells, while induced early at high magnitude, do not develop into functional effectors capable of controlling virus. This defect was partially alleviated by short-term treatment with an HCV antiviral. Thus, like HCV, RHV triggers dysfunction of virus-specific CD8 T cells that are vital for infection resolution. Additional study of this evasion strategy and how to mitigate it could enhance our understanding of hepatotropic viral infections and lead to improved vaccines and therapeutics.

Source: Journal of Virology

DOI: 10.1128/jvi.00035-20

Authors: Alex S. Hartlage, Christopher M. Walker, Amit Kapoor

Institutions: Nationwide Children's Hospital, Abigail Wexner Research Institute, The Ohio State University

Language: English

Topic: Hepatitis C virus research

Subfield: Hepatology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Nationwide Children's Hospital, Research Institute, Nationwide Children's Hospital, National Institute of Allergy and Infectious Diseases