Epitopes described in "The size of the viral inoculum contributes to the outcome of hepatitis B virus infection."

Article Authors:Shinichi Asabe; Stefan F Wieland; Pratip K Chattopadhyay; Mario Roederer; Ronald E Engle; Robert H Purcell; Francis V Chisari
Article Title:The size of the viral inoculum contributes to the outcome of hepatitis B virus infection.
Reference Detail
Reference ID:1026035
Abstract:The impact of virus dose on the outcome of infection is poorly understood. In this study we show that, for hepatitis B virus (HBV), the size of the inoculum contributes to the kinetics of viral spread and immunological priming, which then determine the outcome of infection. Adult chimpanzees were infected with a serially diluted monoclonal HBV inoculum. Unexpectedly, despite vastly different viral kinetics, both high-dose inocula (10(10) genome equivalents [GE] per animal) and low-dose inocula (10 degrees GE per animal) primed the CD4 T-cell response after logarithmic spread was detectable, allowing infection of 100% of hepatocytes and requiring prolonged immunopathology before clearance occurred. In contrast, intermediate (10(7) and 10(4) GE) inocula primed the T-cell response before detectable logarithmic spread and were abruptly terminated with minimal immunopathology before 0.1% of hepatocytes were infected. Surprisingly, a dosage of 10(1) GE primed the T-cell response after all hepatocytes were infected and caused either prolonged or persistent infection with severe immunopathology. Finally, CD4 T-cell depletion before inoculation of a normally rapidly controlled inoculum precluded T-cell priming and caused persistent infection with minimal immunopathology. These results suggest that the relationship between the kinetics of viral spread and CD4 T-cell priming determines the outcome of HBV infection.
Affiliations:Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California 920371, USA.
Reference Type:Literature
PubMed ID:19625407
Journal:J Virol
Journal Volume:83
Article Pages:9652-62
Journal ISSN:1098-5514
Article Chemical List:DNA, Viral;Interferon-gamma
Article MeSH List:Animals; CD4-Positive T-Lymphocytes(virology); DNA, Viral(metabolism); Flow Cytometry(methods); Hepatitis B(virology); Hepatitis B virus(metabolism; pathogenicity); Hepatocytes(virology); Interferon-gamma(metabolism); Kinetics; Leukocytes, Mononuclear(virology); Liver(virology); Pan troglodytes
Curation Last Updated:2015-06-05 04:01:39