Experimental infection of the woodchuck (Marmota monax monax) with woodchuck hepatitis virus

Abstract

Six woodchucks, 10 1/2 months of age, injected intramuscularly with 0.02 ml of woodchuck hepatitis virus (WHV)-positive serum and two woodchucks of similar age and origin injected with phosphate buffered saline were studied by serial blood samples and liver biopsy sections over an 18 week period. Serum samples were assayed for WHV surface antigen (WHsAg), its corresponding antibody (anti-WHs) and antibody to WHV core antigen (anti-WHc). WHV core antigen (WHcAg) was detected in liver biopsy sections by fluorescent labeled anti-WHc, and WHsAg was detected by the Victoria blue stain. All six experimentally infected woodchucks eventually developed anti-WHs and four developed serologic and histologic signs of acute hepatitis. Hepatic lesions resembled lesions described in the livers of chimpanzees and humans with acute hepatitis B viral infections. The first histologic signs of liver change coincided with the appearance of WHsAg within the serum and WHcAg within the cytoplasm of hepatocytes. After WHcAg was no longer detected in the serum, WHsAg appeared in the cytoplasm of hepatocytes. Microfocal areas of hepatic necrosis were associated with aggregates of lymphocytes, macrophages, and a few neutrophils and plasma cells. The periportal exudate became increasingly abundant during the 18-week study period in the four animals with acute hepatitis. The results from this study indicate that acute hepatitis may be induced in the woodchuck by experimental infection with WHV. Furthermore, the woodchuck might serve as an excellent model for the study of the pathogenesis of acute viral hepatitis in man.