Characterization of the immune response against hepatitis C infection in recovered, and chronically infected chimpanzees.
The immune response to hepatitis C virus (HCV) is believed to be critical in determining the outcome of the disease. In this study we have analysed epitope recognition, cytokine profile, and anti-HCV antibody responses in chronically HCV-infected and recovered chimpanzees. Quantitative measurement of anti-HCV antibody in HCV-infected chimpanzees revealed that the response in HCV- recovered chimpanzees peaked within 4-20 weeks. In contrast, the anti-HCV antibody responses in chronically HCV infected chimpanzees did not peak until 100-200 weeks after infection, and decreased gradually thereafter. T cell proliferation assays measuring responses to pooled HCV proteins revealed significant increases in the 3H-uptake during the early stages of infection in recovered chimpanzees in comparison to the chronically infected ones. Class I-restricted epitopes of the core, and NS3 proteins of HCV were analysed using 9-10 mer overlapping peptides covering the core and NS3 proteins, and IFN-gamma ELISPOT technique. Our data indicated early and broad class-I restricted core, and NS3 protein epitope recognitions in HCV-recovered chimpanzees but not in chimpanzees that had been chronically infected. Additionally, dominant epitopes recognized early in infection (8 weeks) were no longer recognized later in infection (followed up to 64 weeks). Cytokines profiling revealed a 50-fold increase in TNF-alpha secretion in the supernatant of core-specific CD8 memory cells of the chronically infected chimpanzees in comparison to the recovered ones. In summary, multiple parameters correlate with HCV recovery in chimpanzees.
Shata
M T
MT
New York Blood Center, Lindsley F. Kimball Research Institute, Virology Laboratory, New York 10021, USA. mohamed.shata@NYBC.org
Anthony
D D
DD
Carlson
N L
NL
Andrus
L
L
Brotman
B
B
Tricoche
N
N
McCormack
P
P
Prince
A
A
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte; D005260:Female; D016174:Hepacivirus / Q000276:immunology; D006526:Hepatitis C / Q000276:immunology* / Q000821:virology; D018937:Hepatitis C Antibodies / Q000097:blood; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000821:virology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D008297:Male; D002679:Pan troglodytes; D010455:Peptides / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014758:Viral Core Proteins / Q000737:chemistry / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000276:immunology; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D018984:Epitopes, T-Lymphocyte; D018937:Hepatitis C Antibodies; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D014758:Viral Core Proteins; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases