Basic–liver, pancreas, and biliary tractHepatitis C Virus Continuously Escapes From Neutralizing Antibody and T-Cell Responses During Chronic Infection In Vivo
Section snippets
Antibodies, Cells, and Reagents
Both 293T and Hep3B cells were propagated in Dulbecco’s modified Eagle medium with 10% fetal bovine serum. Antibodies against HCV E2 have been described previously.14, 23 To generate soluble CD81 an expression plasmid encoding the CD81 large extracellular loop fused to Glutathione S-transferase (GST) was transformed into Rosetta-gami Escherichia coli (Novagen, La Jolla, CA). Fusion proteins were prepared by lysis with an Avestin (Avestin, Ottawa, Canada) air emulsifier (3 passages at 15,000
Clinical Information
Patient H, the subject of this study, was infected with HCV through a blood transfusion in 1977 while undergoing cardiac surgery. After an initial high alanine aminotransferase peak (2112 IU/L), indicative of severe acute hepatitis, he went on to develop mild chronic hepatitis with persistently low alanine aminotransferase levels and HCV RNA levels in the 104 and 106 genome copies/mL range over the following 26 years (Figure 1A). Patient H underwent liver biopsy procedures on 4 occasions, each
Discussion
This study is an in-depth analysis of the nAb response against autologous HCV E1E2 sequences and shows ongoing evasion of the virus-specific adaptive immune response during persistent infection. Patient H is a uniquely well-suited subject for this study because he is representative of many patients with mild, chronic hepatitis C and clinically is well characterized with serum samples spanning a long period of time. Furthermore, specific research tools such as sequences, infectious clones,
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Supported by PHS grants CA57973, AI50798, U19 AI40034, Medical Research Council, UK (G0400802), the National Institute of Diabetes and Digestive and Kidney Diseases intramural research program, the Greenberg Medical Research Institute, and the Starr Foundation. T.v.H. is supported by a postdoctoral fellowship from the Deutsche Forschungsgemeinschaft.