EXPERIMENTAL INFECTION OF COMMON MARMOSET WITH EASTERN EQUINE ENCEPHALITIS VIRUS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Eastern Equine Encephalitis (EEE) virus is an alphavirus that causes disease in humans, horses and birds. The virus in endemic in the Eastern United states and is transmitted by a mosquito resulting in mostly asymptomatic infections in humans. Those that develop symptoms experience flu-like symptoms to encephalitis, coma and death. The overall mortality for those that develop EEE is 30% while those that recover have mild to severe neurologic damage. Because of the potential to use this agent as a biological weapon, the virus is designated as a select agent. There are currently no adequate nonhuman primate models available to test vaccines or therapeutic interventions for the disease. The current study seeks to develop the common marmoset as a model for EEE. A total of three animals were experimentally inoculated with 106 pfu of a North American strain (pathogenic strain) of EEEV by intranasal instillation. A second group of three animals was inoculated with 106 pfu of a South American EEEV strain (nonpathogenic strain) by the same route. Animals were observed daily for up to 15 days post infection. Blood was collected at predetermined time points for hematology and biochemical analysis while temperature data was collected at every blood collection time point. Those animals that were inoculated with the North American strain experienced elevated temperature (104 degrees F) and developed anorexia, depression and neurological signs of disease. Animals become severely moribund by day 5 and were humanely euthanized. Virus was not recovered from blood and was only detected in brain tissue. Examination of H&E stained tissue sections revealed meningoencephalitis. In contrast, those animals inoculated with South American EEEV experienced no elevation in basal temperature and showed no clinical signs of illness. Transient viremia was detected beginning at 24 hours post inoculation peaking at 103 pfu/ml by day 4. No virus was detected in the blood after day 7 post infection. Animals remained healthy until project end of 15 days. The preliminary data from the pilot study provides evidence to support the utility of the common marmoset as a model for EEE.