Characterization of aggregates of hepatitis C virus glycoproteins

Hepatitis C virus (HCV) encodes two glycoproteins, E1 and E2, which assembl e in oligomeric structures. Studies of HCV glycoprotein assembly using hete rologous expression systems have shown that these glycoproteins can follow two pathways: a productive pathway leading to the formation of a non-covale nt heterodimer; and a non-productive pathway leading to the formation of la rge disulfide-linked aggregates. The non-covalent HCV glycoprotein complex is probably the functional complex which plays an active role in the entry process in host cells. The aggregates are believed to be waste products; ho wever, one can imagine that, in infected cells, they could provide HCV glyc oproteins with additional functions. To further understand the potential ro le played by HCV glycoprotein aggregates in HCV infection, a MAb (H14) was produced which specifically recognizes these aggregates but not the non-cov alent E1E2 heterodimer. The H14 epitope was shown to be present on both HCV glycoproteins and was sensitive to deglycosylation, An additional characte rization of HCV glycoprotein aggregates, with the help of MAb H14, indicate s that they share an epitope with a cellular protein called Mac-2 binding p rotein. The presence of such an epitope on HCV glycoprotein aggregates coul d potentially lead to the production of autoantibodies recognizing Mac-2 bi nding protein in HCV-infected patients.