Long-term serological follow up and cross-challenge studies in rhesus monkeys experimentally infected with hepatitis E virus

Background/Aims: The aims of this study were to examine the decline of IgG anti-HEV antibodies over a period of 7 years in rhesus monkeys experimental ly infected with hepatitis E virus, and to assess the protectivity of these antibodies by challenging the monkeys with a heterologous isolate of hepat itis E virus, 5 years after the primary inoculation. Methods: Nine rhesus monkeys (six non-pregnant and three pregnant at the ti me of hepatitis E virus inoculation) were followed serologically and bioche mically for 7 years post-inoculation. Based on regression analysis, estimat ed time for IgG anti-HEV titers to reach 1:100 or 1:50 was calculated, Thre e of the monkeys inoculated initially with AKL-90 isolate and challenged 2 years later with PUN-85 isolate of hepatitis E virus were rechallenged with KOL-91 isolate of the virus, 5 years post-primary inoculation. Evidence of viral replication was assessed by measuring serum alanine aminotransferase levels, excretion of the virus in feces or bile (reverse-transcription pol ymerase chain reaction) and rise in IgG anti-HEV titers (ELISA), Results: None of the challenged monkeys showed evidence of disease. In cont rast to extensive replication of the virus in anti-HEV-negative control mon keys, limited replication was noted in one of the challenged monkeys. The e stimated time for the titers to reach 1:100 or 1:50 varied from 3.15 to 44. 9 years (19.4+/-11.6 years) and 6.9 to 84.3 years (35.4+/-21.3 years), resp ectively, Decline in titers was independent of the pregnancy status at the time of infection or reexposure of the monkeys to HEV; Conclusion: The results show persistence of IgG anti-HEV antibodies for a l ong time and protectivity of low titered antibodies against reinfection, le ading to disease even after intravenous exposure to a heterologous isolate of hepatitis E virus.