UNIVERSITY OF NORTHERN COLORADO
Experimental Tacaribe Virus Infection of Jamaican Fruit Bats: Bats have recently been implicated as reservoirs or potential reservoirs of several human pathogens, including ebolaviruses, marburgviruses, SARS coronavirus, and Nipah and Hendra paramyxoviruses. Tacaribe virus (TCRV), an arenavirus that is closely related to the South American hemorrhagic fever viruses, has only been isolated from Artibeus fruit bats in the Caribbean. We have recently established a colony of one of these species, the Jamaican fruit bat (Artibeus jamaicensis), and have conducted experimental infections with TCRV. High-dose inoculation resulted in neurological symptoms resembling that of Argentine hemorrhagic fever, which is caused by Junin virus. Beginning on day 11, bats appeared lethargic with many exhibiting neurological tremors, some with hemorrhages, and died or were euthanized shortly thereafter. By day 18 all remaining bats exhibited symptoms and were humanely euthanized. Histological evaluation showed that many of the bats had liver, cardiac and pulmonary pathology and PCR and virus isolation showed disseminated viral infection. Low-dose inoculation does not cause pathology, but some bats appeared to remain infected for at least 45 days, suggesting persistence. The work proposed here will focus on further characterization of the pathological events or persistence of infection and how the immune response engages the virus. Our interest in this model is two-fold: (1) as a system to study bats as potential reservoirs and vectors of infectious diseases and (2) as a model for arenavirus pathology. AIM 1: To determine the pathology of Tacaribe virus infection of Jamaican fruit bats. Hypothesis: Tacaribe virus induces pathology similar to that of human infections with South American hemorrhagic fever viruses. We will experimentally infect bats and scrutinize infection more closely to determine sites of virus replication by IHC and quantification of viral load in cell culture. AIM 2: To characterize the immune response during infection. Hypothesis: The immune response contributes to pathogenesis in high-dose infections. We will generate virus-specific T cell lines from pathogenic and nonpathogenic infections and assess immune gene expression to identify which genes might contribute to pathogenesis and determine how faithfully the model resembles the South American hemorrhagic fevers.