CD81 nucleotide mutation in hepatocellular carcinoma and lack of CD81 polymorphism in patients at stages of hepatitis C virus infection

Mechanisms determining the chronicity or the pattern of clinical course of hepatitis C virus (HCV) infections have not been clarified. Recently, CD81 was reported to bind the E2 protein of HCV and was suggested to function as a cellular receptor for HCV. Accordingly, the hypothesis was examined that CD81 polymorphism, if it exists, might correlate with certain clinical cou rses of HCV infection. CD81 cDNA sequences were determined from peripheral blood mononuclear cells (PBMCs). Twenty-four Japanese subjects were enrolle d initially as follows: patients with chronic hepatitis C without cirrhosis (n = 3), patients with cirrhosis (n = 3), patients with cirrhosis complica ted by hepatocellular carcinoma (HCC) (n = 3), patients with persistent HCV viremia without ALT elevation (n = 3), those with positive anti-HCV antibo dies without evidence of HCV viremia (n = 3), and healthy volunteers (n = 9 ). In all PBMCs samples analyzed, no polymorphism was found in the CD81 cDN A sequence. The sequence was different, however, from the one reported prev iously at three nucleotide positions: a transversion to thymine instead of cytosine at nt 1130, a deletion at nt 1206, and a guanine insertion at nt 7 1. Subsequently, CD81 cDNA sequences from PBMCs and HCC tissue were compare d among the other 6 patients with chronic hepatitis C bearing HCC. A compar ative study of the CD81 sequences from HCC and PBMCs revealed that various nucleotide mutations existed only in the HCC samples in 3 out of 6 patients . Several mutations in the 3' non-coding region of CD81 cDNA were observed exclusively in HCC tissue suggesting its possible role in hepatocarcinogene sis. Because of the absence of polymorphisms, however, CD81 is unlikely to affect the progression of chronic hepatitis C in terms of chronicity, hepat itis activity, or disease stage. (C) 2000 Wiley-Liss, Inc.