LINEAR B-CELL EPITOPES OF THE NS3-NS4-NS5 PROTEINS OF THE HEPATITIS-CVIRUS AS MODELED WITH SYNTHETIC PEPTIDES

A set of 150 synthetic peptides spanning the proteins NS3-NS4-NS5 of t he hepatitis C virus (HCV) was synthesized and tested with a panel of 20 sera obtained from HCV-infected patients. Of 62 peptides prepared f rom the NS3 region, none exhibited strong antigenic reactivity. Rather , five peptides from this region demonstrated specific reactivity with only 5-10% of anti-HCV-positive sera. Nonetheless, it is well known t hat the NS3 region contains strong antigenic epitopes. These epitopes appear to be modeled in a functionally active manner with recombinant proteins and cannot be mimicked properly with short synthetic peptides . This finding suggests that the major NS3 antigenic epitopes are conf ormationally dependent. Seven of 20 peptides prepared from the NS4 reg ion were immunoreactive. Five peptides from this region demonstrated v ery strong HCV-specific antigenic reactivity, Four of the five peptide s belong to the recognized immunoreactive 5-1-1 region located inside the C100-3 antigen. One peptide demonstrating immunoreactivity with ap proximately 90% of anti-HCV-positive sera was found outside the C100-3 region at the C-terminal part of the NS4 protein. Of 68 peptides synt hesized from the NS5 protein, 30 were immunoreactive. Six of the 30 de monstrated immunoreactivity with 35-50% of anti-HCV-positive sera. Thu s, the NS4 and NS5 regions of the HCV polyprotein contain a large numb er of specific, broadly reactive, linear antigenic epitopes. The highl y antigenic reactivity of the NS5 region suggests that this protein ma y have significant diagnostic potential. (C) 1995 Academic Press, Inc.