Nonenveloped nucleocapsids of hepatitis C virus in the serum of infected patients

One of the characteristics of hepatitis C virus (HCV) is the high incidence of persistent infection. HCV core protein, in addition to forming the vira l nucleocapsid, has multiple regulatory functions in host-cell transcriptio n, apoptosis; cell transformation, and lipid metabolism and may play a role in suppressing host immune response. This protein is thought to be present in the bloodstream of the infected host as the nucleocapsid of infectious, enveloped virions. This study provides evidence that viral particles with the physicochemical, morphological, and antigenic properties of nonenvelope d HCV nucleocapsids are present in the plasma of HCV-infected individuals. These particles have a buoyant density of 1.32 to 1.34 g/ml in CsCl, are he terogeneous in size (with predominance of particles 38 to 43 or 54 to 62 nm in diameter on electron microscopy), and express on their surface epitopes located in amino acids 24 to 68 of the core protein. Similar nucleocapsid- like particles are also produced in insect cells infected with recombinant baculovirus bearing cDNA for structural HCV proteins. HCV core particles is olated from plasma were used to generate anti-core monoclonal antibodies (M Abs). These MAbs stained HCV core in the cytoplasm of hepatocytes from expe rimentally infected chimpanzees in the acute phase of the infection. These chimpanzees had concomitantly HCV core antigen in serum. These findings sug gest that overproduction of nonenveloped nucleocapsids and their release in to the bloodstream are properties of HCV morphogenesis. The presence of cir culating cores in serum and accumulation of the core protein in liver cells during the early phase of infection may contribute to the persistence of H CV and its many immunopathological effects in the infected host.