Hepatitis B virus replication in diverse cell types during chronic hepatitis B virus infection

Authors

  • Andrew Mason,

    1. Gastroenterology Section, Veterans Affairs Medical Center, St. Louis, Missouri 63106
    2. Department of Internal Medicine, Washington University, St. Louis, Missouri 63110
    Search for more papers by this author
  • Mark Wick,

    1. Department of Pathology, Washington University, St. Louis, Missouri 63110
    Search for more papers by this author
  • Heather White,

    1. Department of Internal Medicine, Washington University, St. Louis, Missouri 63110
    Search for more papers by this author
  • Robert Perrillo M.D.

    Corresponding author
    1. Gastroenterology Section, Veterans Affairs Medical Center, St. Louis, Missouri 63106
    2. Department of Internal Medicine, Washington University, St. Louis, Missouri 63110
    • St. Louis Veterans Affairs Medical Center (111 JC), 915 North Grand Blvd., St. Louis, MO 63106
    Search for more papers by this author

Abstract

Hepatitis B virus–specific nucleic acid sequences and proteins have been detected in extrahepatic tissues of acutely and chronically infected patients. However, apart from peripheral blood mononuclear cells and bone marrow cells, little is known about the specific cell types that permit viral replication. In this study, we assessed the extrahepatic tissues of four patients who died with chronic hepatitis B virus infection and two uninfected controls by means of in situ hybridization and immunohistochemical study. Three of these patients had diffuse extrahepatic distribution of the virus. Hepatitis B virus nucleic acid sequences and proteins were detected in the lymph nodes, spleen, bone marrow, kidney, skin, colon, stomach, testes and periadrenal ganglia. The following cell types were found to be positive for hepatitis B virus: endothelial cells, macrophages/monocytes, hematopoietic precursors, basal keratinocytes, mucosal epithelial cells, stromal fibroblasts and sustentacular and neuronal cells. It is probable that these cells could support viral replication because hepatitis B virus DNA replicative intermediates, viral transcripts and HBsAg and HBcAg proteins were detected in most. These findings may be relevant to the initiation of extrahepatic syndromes associated with chronic hepatitis B virus infection such as vasculitis, glomerulonephropathy, neuropathy and dermatitis. (HEPATOLOGY 1993;18:781-789).

Ancillary