Hepatocytes of double-transgenic mice expressing high levels of hepatitis B virus e antigen and interferon-γ are not injured by HBeAg specific autoantibodies

• Published in: Archives of virology 2000-01, Vol.145 (6), p.1081-1098
• Main Authors: MERKLE, H, NUSSER, P, KNEHR, S, LÖHLER, J, BARSIG, J, YAMAMURA, K.-I, REIFENBERG, K
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antibody Specificity; Autoantibodies; Autoantibodies - blood; Autoantibodies - immunology; Biological and medical sciences; Cell Line; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Hepatitis B; Hepatitis B - immunology; Hepatitis B - pathology; Hepatitis B - virology; Hepatitis B Antibodies - blood; Hepatitis B e antigen; Hepatitis B e Antigens - immunology; Hepatitis B e Antigens - metabolism; Hepatocytes; Interferon; Interferon-alpha - biosynthesis; Interferon-alpha - immunology; Interferon-gamma - biosynthesis; Interferon-gamma - immunology; Liver - cytology; Liver - immunology; Liver - pathology; Liver - virology; Liver diseases; Macrophages; Mice; Mice, Transgenic; Microbiology; Protein Precursors - metabolism; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Rodents; Seroconversion; Transfection; Transgenic animals; Transgenic mice; Tumors; Viral Core Proteins - metabolism; Virology; γ-Interferon
• ISSN: 0304-8608; 1432-8798
• DOI: 10.1007/s007050070111

Seroconversion from HBeAg to alphaHBe of persons chronically infected by HBV is usually associated with a transient exacerbation of liver disease and subsequent normalization of liver histology. It is speculated that these clinico-pathological features may be due to the activation of cytodestructive mechanisms by alphaHBe antibodies. The aim of the present study was to investigate the pathogenic potential of alphaHBe antibodies in a transgenic mouse model. Therefore, alphaHBe autoantibodies were elicited in double-transgenic mice expressing high amounts of HBeAg and interferon-gamma in the liver. Interferon-gamma has reviously been shown to play an important role in the development of hepatic necroinflammation associated with hepadnaviral infection, probably via tumor-necrosis-factor-alpha secreted by activated macrophages. We found no evidence that alphaHBe antibodies have the potential to destroy HBeAg-secreting hepatocytes even if the cells were predisposed to injury due to high-level interferon-gamma expression. We conclude that seroconversion from HBeAg to alphaHBe of persons chronically infected with HBV seems to be an immunological epiphenomenon without pathogenic significance.