Studies on transmission of hepatitis A virus to squirrel monkeys

Non-human primates have been playing an essential role in the study of hepa titis A virus (HAV) biology, pathogenesis and for testing candidate HAV vac cines. This study was to determine the suitability of squirrel monkeys (Sai miri sciureus) as animal model for HAV infection. Animals were inoculated, either intragastrically or intravenously, with a Brazilian HAV isolate (HAF -203). Alanine aminotransferase (ALT) and anti-HAV antibodies (IgM and tota l) were monitored. Feces were daily collected for HAV antigen and HAV RNA d etection. Samples of liver tissue were obtained by biopsy before inoculatio n, at peak ALT levels and/or when anti-HAV antibodies developed, and at nec ropsy for morphological examination. Monkeys inoculated by the intravenous route rapidly developed significant elevations of serum ALT, anti-HAV antib odies, and liver histologic changes, while the only evidence of HAV infecti on in intragastrically inoculated animals was the seroconversion. Moreover, squirrel monkeys excreted very low levels of HAV detectable in only few fe cal samples after amplification by RT-PCR, different from humans and other non-human primate species that eliminate large quantities of virus during t he late incubation period. The unusual onset of hepatitis A in experimental ly infected squirrel monkeys represent an important obstacle for its use as animal model for the study of this viral infection. However, they can repr esent a valuable tool for the obtention of hyperimmune sera for HAV, in the view of the very high titer of anti-HAV developed (10(5)) 24 days after a single intravenous inoculation.