Experimental HBV and δ infections of chimpanzees: Occurrence and significance of intrahepatic immune complexes of HBcAg and δ antigen

Authors

  • Mario Rizzetto M.D.,

    Corresponding author
    1. Division of Molecular Virology and Immunology, Georgetown University Medical Center, Rockville, Maryland 20850
    2. Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20205
    3. Infectious Diseases Branch, National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20205
    4. Meloy Laboratories, Rockville, Maryland 20850
    • Department of Gastroenterology, Ospedale S. Giovanni, Torino, Italy
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  • Maria G. Canese,

    1. Division of Molecular Virology and Immunology, Georgetown University Medical Center, Rockville, Maryland 20850
    2. Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20205
    3. Infectious Diseases Branch, National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20205
    4. Meloy Laboratories, Rockville, Maryland 20850
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  • Robert H. Purcell,

    1. Division of Molecular Virology and Immunology, Georgetown University Medical Center, Rockville, Maryland 20850
    2. Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20205
    3. Infectious Diseases Branch, National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20205
    4. Meloy Laboratories, Rockville, Maryland 20850
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  • William T. London,

    1. Division of Molecular Virology and Immunology, Georgetown University Medical Center, Rockville, Maryland 20850
    2. Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20205
    3. Infectious Diseases Branch, National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20205
    4. Meloy Laboratories, Rockville, Maryland 20850
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  • L. David Sly,

    1. Division of Molecular Virology and Immunology, Georgetown University Medical Center, Rockville, Maryland 20850
    2. Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20205
    3. Infectious Diseases Branch, National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20205
    4. Meloy Laboratories, Rockville, Maryland 20850
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  • John L. Gerin

    1. Division of Molecular Virology and Immunology, Georgetown University Medical Center, Rockville, Maryland 20850
    2. Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20205
    3. Infectious Diseases Branch, National Institute of Neurological and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20205
    4. Meloy Laboratories, Rockville, Maryland 20850
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Abstract

The occurrence and pathogenetic role of intrahepatic deposits of immunoglobulins in experimental viral infection have been evaluated by determining with immunofluorescence their capacity to fix complement in vitro [in vitro complement fixation (VCF)]. Liver biopsies from chimpanzees chronically or acutely infected with hepatitis B virus or the hepatitis B surface antigen (HBsAg)-associated δ agent were used in the study. VCF was observed in each animal expressing hepatitis B core antigen (HBcAg) or δ antigen in the liver and concurrently circulating the homologous antibody in the blood. In acutely infected animals, VCF appeared at the same time that the homologous serum antibody appeared, and the intensity of VCF staining was proportional to the antibody titer in the serum. In animals expressing sequentially the HBcAg/antibody system and then δ antigen and antibody to δ, VCF was first observed in HBcAg-containing nuclei and then in nuclei expressing δ antigen. There was no relationship between VCF and intrahepatic expression of HBsAg or serologic expression of hepatitis B e antigen (HBeAg).

A positive VCF reaction appears related to the formation of intrahepatic immune complexes between HBcAg or δ antigen and the homologous antibody. Although acute hepatitis developed in parallel with the occurrence of VCF in two animals, strong VCF fluorescence was also observed in each of the asymptomatic carriers of HBsAg, and, in one of them, preexisting VCF staining of HBcAg disappeared in parallel with development of acute hepatitis.

In experimentally infected chimpanzees, the finding in liver biopsies of immune complexes detectable by VCF appears to be a common epiphenomenon without pathogenic significance.

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