Hepatic HLA antigen display in chronic hepatitis B virus infection. Relation to hepatic expression of HBV genome/gene products and liver histology.
To determine the relationship between hepatitis B virus (HBV) replication and HLA antigen display at a cellular level, the hepatic expression of HLA antigens and HBV genome (HBV-DNA)/gene products (HBsAg/HBcAg) was studied in 24 patients with chronic HBV infection using simultaneously immunohistochemistry and nonisotopic in situ hybridization. The effect of interferon-alpha and interferon-gamma on hepatocyte HLA antigen expression was also evaluated using primary hepatocyte culture in eight patients with chronic HBV infection. HLA class I antigens were detected on hepatocyte membrane in 23 patients (95.8%). Hepatocytes positive for HBcAg and HBV-DNA (cytoplasmic +/- nuclear) were either negative or only faintly positive for HLA class I antigens, while hepatocytes positive for HBsAg showed similar levels of HLA class I antigen expression compared with those hepatocytes with no HBsAg expression. In contrast, hepatocytes adjacent to inflammatory infiltrates, whether positive for HBV-DNA or HBV antigens or not, were always strongly positive for HLA class I antigens. Furthermore, active liver histology (N = 12) was associated with a higher overall level of hepatic HLA class I antigen expression as compared with inactive histology (N = 12, P = 0.003). Both interferon-alpha and interferon-gamma treatment in vitro enhanced hepatocyte HLA class I antigen expression. These data indicate that expression of HLA class I antigens is not enhanced on the membrane of hepatocytes with HBV replication, and this may be one factor that permits the development of viral persistence.
Lau
J Y
JY
Department of Medicine, University of Florida, Gainesville 32610.
Bird
G L
GL
Naoumov
N V
NV
Williams
R
R
D000328:Adult; D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D016679:Genome, Viral; D006680:HLA Antigens / Q000032:analysis*; D006509:Hepatitis B / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D006511:Hepatitis B Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000235:genetics* / Q000302:isolation & purification; D006521:Hepatitis, Chronic / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007372:Interferons / Q000494:pharmacology; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D014764:Viral Proteins / Q000032:analysis*
D004279:DNA, Viral; D006680:HLA Antigens; D006511:Hepatitis B Antigens; D015395:Histocompatibility Antigens Class I; D014764:Viral Proteins; D007372:Interferons