IMMUNE-RESPONSE TO AN EPITOPE OF THE NS4 PROTEIN OF HEPATITIS-C VIRUSIN HCV-RELATED DISORDERS

NS4, a nonstructural protein of HCV, is a frequent target of antibodie s in infected subjects. According to recent data, the antibodies frequ ently recognize the sequence 1921-40 of the NS4 protein. The aim of th is work was to analyze antibody reactivity with the sequence 1921-40 i n different HCV-related disorders. Although this sequence is located i n a relatively invariant region of viral genome, two strain-specific s equences are described. Thus, three NS4 1921-1940 peptides were synthe sized: the BR shared by most viral strains, the J6 (strain 2a), and th e J8 (strain 2b). The peptides were used as antigens in the solid phas e for measuring serum IgG antibodies in an ELISA assay. Antibodies rea ctive with the 1921-40 BR peptide were detected in 64% of sera from pa tients with autoimmune hepatitis (AIH), 51% from chronic hepatitis C ( CHC), and 22% from mixed cryoglobulinemia (MC). The frequency of posit ive sera in MC was significatively lower than in AIH (P < 0.0001) or C HC (P < 0.0021). Similar results were obtained with the J6 and J8 pept ides. All sera that did not react with the BK peptide were negative oi l J6 and J8 and conversely most sera reacting with the BK peptide also bound the J6 and the J8 peptides. No correlation was found between th e genotype of the infecting virus and the presence of antibodies to an y of the NS4 peptides. These results indicate that many HCV-infected s ubjects produce antibodies to the NS4 sequence 1921-40. The immune res ponse to this sequence is not strain specific and varies with the diff erent disorders associated with HCV infection. (C) 1998 Academic Press .