Temporal changes in pathology and viral RNA distribution in guinea pigs following separate infection with two New World Arenaviruses

Numerous arenaviruses have been identified throughout the Americas and a subset of these viruses cause viral hemorrhagic fever in humans. This study compared the pathology and viral RNA distribution in Hartley guinea pigs challenged with two human-disease causing New World arenaviruses, Junin virus (JUNV) or Guanarito virus (GTOV). Histopathologic analysis and RNA in situ hybridization revealed similar pathology and viral RNA distribution for both groups of animals challenged with either JUNV or GTOV on days 3, 7, 10 and 12 post exposure (PE). Gross lesions were first observed on day 7 and primarily involved the lungs and liver. The most severe histologic lesions occurred in the lymph nodes, spleen, and thymus and included lymphoid depletion and necrosis which increased in severity over time. Extensive necrosis was also observed in the bone marrow on day 12. Minimal to mild inflammation with and without necrosis was observed in the choroid plexus of the brain, choroid of the eye, intestinal tract, lung and adrenal gland. Significant liver lesions were rare, consisting predominantly of hepatocyte vacuolation. Viral RNA labeling was identified in nearly all organs examined, was often extensive in certain organs and generally increased over time starting on day 7. Our data demonstrate the guinea pig may serve as a useful model to study New World arenavirus infection in humans and for the evaluation and development of medical countermeasures.