Pirital virus (arenaviridae) infection in the Syrian golden hamster, Mesocricetus auratus: A new animal model for arenaviral hemorrhagic fever

Adult Syrian golden hamsters inoculated intraperitoneally with Pirital viru s, a recently discovered member of the Tacaribe complex of New World arenav iruses, developed a progressively severe, fatal illness with many of the pa thologic features observed in fatal human cases of Lassa fever and other ar enaviral hemorrhagic fevers. Most of the animals became moribund by Day 5 a nd were dead by Day 7 after inoculation. The most consistent histopathologi c changes included interstitial pneumonitis, splenic lymphoid depletion and necrosis, and multifocal hepatic necrosis without significant inflammatory cell infiltration. The liver changes ranged from single cell death by apop tosis to coagulative necrosis of clusters of hepatocytes. Immunohistochemic al studies of the liver demonstrated the presence and accumulation of Pirit al virus antigen within hepatocytes as well as Kupffer cells. An in situ te rminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay showed progressively increasing apoptotic activity in the liver of i nfected hamsters. A human hepatoblastoma cell line (Hep G2/C3A) inoculated with Pirital virus also developed progressive cell destruction and accumula tion of viral antigen, as demonstrated by immunofluorescence. Results of th is pilot study suggest that the Pirital virus-hamster model is a very promi sing new small animal model for studying the pathogenesis of arenavirus inf ections, particularly, the mechanism of direct virus-induced hepatic injury . It may also be useful for testing antiviral agents for treatment of arena viral hemorrhagic fevers.