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 viral nucleocapsid, has multiple regulatory functions in host-cell transcription, 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 nonenveloped 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 heterogeneous 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 isolated from plasma were used to generate anti-core monoclonal antibodies (MAbs). These MAbs stained HCV core in the cytoplasm of hepatocytes from experimentally infected chimpanzees in the acute phase of the infection. These chimpanzees had concomitantly HCV core antigen in serum. These findings suggest that overproduction of nonenveloped nucleocapsids and their release into the bloodstream are properties of HCV morphogenesis. The presence of circulating cores in serum and accumulation of the core protein in liver cells during the early phase of infection may contribute to the persistence of HCV and its many immunopathological effects in the infected host.

[Humoral response to HBV antigens in acute and chronic hepatitis B]. / Odpowiedz humoralna na antygeny HBV w ostrym i przewleklym wir usowym zapaleniu watroby typu B.

Sera of patients with acute and chronic hepatitis B and antigenemia were tested for the presence of anti-HBe and anti-HBs antibodies, free or bound in immune complexes. The possible occurrence of immune complexes of HBcAg in these sera was also investigated. Immune complexes were identified by antigen specific enzyme immunoassay, in which polyclonal antibodies against synthetic fragments of proteins S and C of HBV and mono- and polyclonal anti-HBc antibodies were used as a solid phase. Free and/or antigen bound anti-HBe antibodies were detected in 100% of patients with acute (81% HBeAg positive) and in 37% of patients with chronic hepatitis, all HBeAg positive. Anti-HBs antibodies or their immune complexes were found in 83% and 37% of patients, respectively. In not any patient circulating complexes of HBcAg could be identified. The results obtained support the observations that humoral immune response to HBeAg and HBsAg can be detected earlier than generally accepted; they also suggest that the detection of anti-HBs in a single sample of serum should not be considered as the evidence of elimination of infection.

[Etiology of chronic hepatitis as evaluated by liver biopsy and serum samples submitted to the Department of Immunopathology of the National Institute of Hygiene in 1993-1995]. / Etiologia przewleklych zapalen watroby na podstawie badan biopsji watroby i surowic nadeslanych do Zakladu Immunopatologii Panstwowego Zakladu Higieny w Latach 1993-1995.

The purpose of this study was to assess the relative incidence of chronic hepatitis in a population of patients with chronic liver disease and to determine the etiological spectrum of this syndrome with special reference to its defined histopathological forms. Histopathology aided by immunohistochemistry, and serology aided by the PCR method were employed in studies of liver biopsy specimens and serum samples, respectively. Out of 1150 patients with chronic liver disease examined, chronic hepatitis was diagnosed in 685 (60% of all cases examined). In this group, there were 308 males aged 18-74 yrs (mean 32 yrs), 153 females aged 18-71 yrs (mean 43 yrs), and 213 children aged 1-17 yrs (mean 8 yrs). Viral infections documented in these patients included HBV (50.4%), HCV (36.2%), HBV/HCV (7.2%) and HBV/HDV (0.7%); cryptogenic and autoimmune hepatitis (AIH) accounted for 2.9% and 2.6% all cases, respectively. In the group of minimal hepatitis (16.1%), HBV infection was documented in 66.4% of cases, HCV-in 29.1%, HBV/HCV-in 3.6% (one case of AIH was included into this group). In the group of mild hepatitis (44.2%), HBV infection accounted for 47.3% of cases, HCV-for 41.9%, HBV/HCV-for 9.9%, and 0.9% was diagnosed as cryptogenic. In the group of moderate hepatitis (19.6%), HBV infection accounted for 50% of cases, HCV-for 37.3%, and HBV/HCV-for 4.5%; cases of cryptogenic and AIH accounted for 3.7% and 4.5%, respectively. In the group of severe hepatitis (20.1%), HBV etiology was found in 44.9% of cases, HCV-in 28.3%, HBV/HCV-in 6.5% and HBV/HDV-in 3.6%; cryptogenic and AIH accounted for 6.5% and 8.0% of cases, respectively. There was a high incidence of low-titer autoantibodies (SMA, ANA and LKM) ranging from 75% in cryptogenic hepatitis and 51% in each HBV and HBV/HCV hepatitis to 46.3% in HCV hepatitis.

[Anti-idiotypic antibodies against antibodies to HBsAg and against antibodies to pre-S1 and pre-S2 fragments of HBV in patients with chronic HBs antigenemia]. / Przeciwciala anty-idiotypowe skierowane przeciwko pezciwcialom dla HBsAg oraz przeciwcialom dla fragmentów pre-S1 i pre-S2 otoczki HBV u chorych z przewlekla antygenemia HBs.

Anti-idiotypic antibodies (anti-Id Ab) against antibodies to HBs, pre-S1 and pre-S2 antigenic domains of the HBV surface protein were searched for by enzyme-linked immunosorbent assay in single serum samples of 57 patients, chronic HBsAg carriers. IgG and/or IgM anti-Id Ab were detected in 15 patients (26%). IgG and / or IgM anti-[anti-HBs] anti-Id Ab were found in 8 serum samples (14%) and they appeared to occur more frequently in patients seropositive for HBeAg than in these seropositive for anti-HBe. IgG and / or IgM anti-[pre-S1] anti-Id Ab and IgG and / or IgM anti-[anti-pre-S2] anti-Id Ab were detected in 5 (9%) and 8 (14%) patients, respectively. Both these anti-Id Ab were found more frequently in patients seropositive for anti-HBe than in patients seropositive for HBeAg. Anti-[anti-pre-S2] anti-Id Ab occurred more frequently in patients with sever liver damage than in these with near normal liver or established cirrhosis.