PATHOGENESIS OF HEPATITIS-A IN ORALLY INOCULATED OWL MONKEYS (AOTUS-TRIVIRGATUS)

The pathogenesis of hepatitis A virus (HAV) infection was studied in o wl monkeys following oral administration of the wild-type HM-175 strai n of HAV. Stools were collected daily and blood and pharyngeal swabs t wice weekly for viral isolation, and animals were necropsied at variou s intervals after inoculation. Organs were examined for the presence o f virus by isolation in cell culture and for viral antigens by immunof luorescence. Monkeys excreted HAV in the stools for 1-4 days after ino culation, presumably due to the residual unabsorbed inoculum. No virus was found in stools for the next 2-3 days. HAV re-appeared on days 4- 7 and then persisted through day 39. Viremia occurred on the 10th day and continued until day 35. Virus was isolated occasionally from throa t swabs 1 or 2 weeks after it was detected in stools and blood, and th ere was no evidence that HAV replicated in the pharyngeal tissues. Ani mals acquired anti-HAV antibody by the 4th week, and alanine aminotran sferase (ALT) was elevated 5-5.5 weeks after inoculation. HAV was isol ated from liver 5 days after inoculation; however, viral antigens were first detected in Kupffer cells of the liver at 14 days and in hepato cytes at 21 days. HAV antigen was detected in epithelial cells of the intestinal crypts and in the cells of the lamina propria of the small intestine 3 days postinoculation and thereafter until the 5th week, su ggesting that these cells might represent an additional site of HAV re plication. (C) 1995 Wiley-Liss, Inc.