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Five cynomolgus monkeys (Macaca fascicularis) developed hepatitis after inoculation with a prototype strain of hepatitis E virus (HEV) from Pakistan. Although all 5 monkeys displayed liver enzyme elevations, viremia, virus secretion in feces, and seroconversion, two different patterns of these parameters were observed. For 4 monkeys, increased alanine aminotransferase (ALT) activity was first observed on days 21-26, viremia occurred before and during enzyme elevation, and the animals seroconverted coincidentally with the end of viremia or shortly thereafter. One of these monkeys had a more severe hepatitis, with peak ALT values more than twice the peak levels of the other monkeys. The fifth monkey developed biphasic hepatitis with peaks of ALT activity on days 26 and 54. In this case, viremia and seroconversion were correlated only with the second peak of enzyme elevation and liver histopathology only with the first peak. Viral shedding in this fifth animal lasted two times longer than in other animals.

Owl and cynomolgus monkeys were inoculated with hepatitis E virus (HEV) to compare disease models and produce antibody and virus. By immune electron microscopy (IEM), all six owl monkeys were shown to have serologic responses manifested by unusually high levels of anti-HEV at 6 months, but only three developed hepatitis. Virus-related antigen in liver (HEV Ag) was detected by immunofluorescence microscopy of biopsies from two of four owl monkeys; one with HEV Ag also had HEV in acute-phase bile (detected by IEM) and feces (detected by infecting another owl monkey). In contrast, cynomolgus monkeys propagated HEV to higher levels and all five had hepatitis. Moderate-to-high levels of HEV Ag correlated with detectable HEV in bile for both species. Thus, the value of using HEV-infected cynomolgus was confirmed. Owl monkeys were shown to be HEV-susceptible and sources of high-level anti-HEV; Sustained anti-HEV in these monkeys may also be useful for understanding immune responses.