Hepatitis C virus c100 antigen in liver tissue from patients with acute and chronic infection

✍ Scribed by Domenico Sansonno; Franco Dammacco

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 789 KB
• Volume: 18
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840180203

✦ Synopsis

A pool of murine monoclonal antibodies developed against clOO antigen, a hepatitis C virus-associated protein encoded by the NS3/NS4 virus genome, was used to detect hepatitis C virus in liver biopsy specimens from patients with acute and chronic hepatitis C virus infection. The antigen was present in the cytoplasm of liver cells only. The immunoreactive signal appeared as large, distinct, brilliant fluorescent granules with no clear relationship to cellular structures. No obvious membrane clOO antigen accumulation was observed. Distribution of c100-containing hepatocytes was directly correlated with viral replication in acute hepatitis. All three acute-hepatitis patients were positive for hepatitis C virus RNA (as detected on polymerase chain reaction) in serum and displayed clOO antigen in 50% to 70% of hepatocytes, with a distinct topographical relationship with necrotic areas and inflammatory cell accumulation. Conversely, very low numbers of infected cells and no relationship between tissue c100 antigen expression and sites of liver cell necrosis and inflammation were found in 14 chronic hepatitis C virus infection patients. Furthermore, though all patients had measurable levels of serum hepatitis C virus RNA, only eight (57%) had detectable clOO antigen in liver sections. Indeed, these two distinct immunopathological patterns were inversely related to the development of c100 antibody in serum. Specificity of hepatocellular clOO antigen deposits was established through extensive absorption experiments using structural and nonstructural hepatitis C virus recombinant proteins. However, tissue processing was found to be a crucial step in the demonstration of hepatitis C virus antigen in fresh frozen liver tissue. Furthermore, monoclonal antibodies against recombinant core and NS3-encoded proteins failed to demonstrate immunofluorescent