Experimental studies on subclinical hepatitis E virus infection in cynomolgus macaques

Serial subclinical transmission among susceptible humans may serve as a reservoir of hepatitis E virus (HEV) in areas in which HEV is endemic. This hypothesis was investigated in an experimental primate model. Four groups of 4 cynomolgus macaques each were inoculated intravenously with 10(4)-10(5) (group 1), 10-100 (group 2), and 1-10 (group 3) cynomolgus macaque HEV infectious doses. All 4 animals in group 1 had clinical disease marked by alanine aminotransferase (ALT) elevation, fecal virus excretion, viremia, and seroconversion. Of the animals in groups 2 and 3, only 1 had evidence of biochemical hepatitis, although most had virus excretion and viremia (3 animals each in groups 2 and 3), and evidence of seroconversion (1 animal in group 2 and 3 animals in group 3). Viral genomic titers in stool specimens of animals with or without ALT elevation were similar. Infectivity studies confirmed the viability and transmission potential of the virus excreted by animals without ALT elevation. These data suggest that subclinical HEV infection may represent an HEV reservoir.