Hepadna virus nucleocapsid and surface antigens and the antigen-specific antibodies associated with hepatocyte plasma membranes in experimental woodchuck acute hepatitis.
Hepatocyte plasma membranes purified from five woodchucks with distinct serologic and histologic patterns of experimentally induced acute woodchuck hepatitis virus (WHV) infection were studied to determine the virus antigens expression and anti-viral specificity of the bound immunoglobulins. WHV core, e, and surface antigens (WHcAg, WHeAg, and WHsAg, respectively) were analyzed with the use of immunoblotting technique both in the native form of these membranes and in the membranes treated with high molar urea or a nonionic detergent. The eluted material was tested either for the presence of WHV antigens or reactivity of the antibodies directed to the virus antigens. The data revealed that acute WHV infection is accompanied by hepatocyte plasma membrane expression of all three viral antigens tested. In all cases, native membranes displayed both WHeAg and WHsAg, whereas WHcAg presence was detected in hepatocyte plasma membranes after their disruption with urea or a detergent. The data indicated that a part or, in some instances, even the whole detectable WHcAg specificity can be incorporated into plasma membrane structure in such a way that it is not accessible for recognition by the specific antibodies (anti-WHc), suggesting at least a partial functional disability of this antigen as a target for immunologic reactions in in vivo conditions. In contrast, WHeAg specificity was detectable in all native membrane preparations studied and its expression was not evidently influenced by the employed treatments, whereas that of WHsAg tended to decline. Further, anti-WHc reactivity was identified in all membrane eluates tested, but antibodies to WHeAg (anti-WHe) were exclusively found in the material eluted from membranes originating from woodchucks with borderline histologic activity of acute hepatitis, which cleared away e antigen from the serum shortly before liver perfusion. Antibodies to WHsAg (anti-WHs) did not show up in the eluates. The present findings demonstrated that WHeAg specificity is not only exposed on the surface of infected hepatocytes, but is also relatively more easily accessible for serologic recognition than that of WHcAg in acute WHV infection. The above observation suggests that e antigen can serve as a potential plasma membrane target for hepatocytolytic attack in addition to that of WHsAg or WHcAg. Moreover, the results of this study demonstrated an apparent relationship between low histologic activity of liver inflammation, e antigen clearance from the circulation, and detectability of hepatocyte plasma membrane-bound anti-e antibodies in acute hepadna viral hepatitis.
Michalak
T I
TI
Liver Research Laboratory, Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
Lin
B
B
Churchill
N D
ND
Dzwonkowski
P
P
Desousa
J R
JR
D000208:Acute Disease; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D002213:Capsid / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology; D015613:Hepadnaviridae / Q000276:immunology*; D006524:Hepatitis, Viral, Animal / Q000276:immunology*; D008099:Liver / Q000276:immunology* / Q000382:microbiology; D008392:Marmota / Q000382:microbiology; D014758:Viral Core Proteins / Q000276:immunology*
D000914:Antibodies, Viral; D000954:Antigens, Surface; D000956:Antigens, Viral; D014758:Viral Core Proteins