Hepatitis B surface antigen binds to human serum albumin cross-linked by transglutaminase

Authors

  • Swan N. Thung M.D.,

    Corresponding author
    1. The Lillian and Henry M. Stratton-Hans Popper Department of Pathology, Mount Sinai School of Medicine, City University of New York, New York, New York 10029
    2. Department of Pathology, Tulane University School of Medicine, New Orleans, Louisiana 70112
    • Department of Pathology, Box 1194, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, New York 10029
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  • De-Fa Wang,

    1. The Lillian and Henry M. Stratton-Hans Popper Department of Pathology, Mount Sinai School of Medicine, City University of New York, New York, New York 10029
    2. Department of Pathology, Tulane University School of Medicine, New Orleans, Louisiana 70112
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  • Thomas M. Fasy,

    1. The Lillian and Henry M. Stratton-Hans Popper Department of Pathology, Mount Sinai School of Medicine, City University of New York, New York, New York 10029
    2. Department of Pathology, Tulane University School of Medicine, New Orleans, Louisiana 70112
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  • Andrew Hood,

    1. The Lillian and Henry M. Stratton-Hans Popper Department of Pathology, Mount Sinai School of Medicine, City University of New York, New York, New York 10029
    2. Department of Pathology, Tulane University School of Medicine, New Orleans, Louisiana 70112
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  • Michael A. Gerber

    1. The Lillian and Henry M. Stratton-Hans Popper Department of Pathology, Mount Sinai School of Medicine, City University of New York, New York, New York 10029
    2. Department of Pathology, Tulane University School of Medicine, New Orleans, Louisiana 70112
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  • This work is dedicated to the memory of Hans Popper, M.D., Ph.D.

Abstract

It has been postulated that polymerized human serum albumin may play a role in the infection of hepatocytes by hepatitis B virus, because both the envelope of hepatitis B virus (HBsAg) and hepatocytes exhibit binding activity for human serum albumin after cross-linking by glutaraldehyde. Since glutaraldehyde-dependent cross-linking of albumin molecules is not likely to occur in vivo, we considered the possibility that albumin may be polymerized by the action of transglutaminase enzymes present in plasma as activated factor XIII or released into plasma from tissues. Guinea pig liver transglutaminase covalently cross-linked human serum albumin molecules into dimers, trimers and polymers up to hexamers as shown by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. HBsAg particles bound transglutaminase-cross-linked as well as glutaralde-hyde-cross-linked human serum albumin as demonstrated by radioimmunoassay and immunoelectron microscopy. The binding was blocked by preincubation of HBsAg with transglutaminase-or glutaraldehyde-cross-linked human serum albumin, anti-HBs or monoclonal anti-pre-S2, but not by polymerized bovine or rat serum albumin or by monomeric human serum albumin. These data indicate that HBsAg particles contain specific binding sites for transglutaminase-cross-linked human serum albumin, but it remains to be determined whether the albumin polymers play a role in the attachment of hepatitis B virus to hepatocytes.

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