Autor: |
Cline, Curtis, Zeng, Xiankun, Bell, Todd M., Shaia, Carl, Facemire, Paul, Williams, Janice, Davis, Neil, Babka, April, Picado, Edwin, Fitzpatrick, Colin, Golden, Joseph W. |
Předmět: |
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Zdroj: |
PLoS Neglected Tropical Diseases; 9/8/2023, Vol. 17 Issue 9, p1-33, 33p |
Abstrakt: |
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. Author summary: Arenaviruses are a type of RNA virus that primarily exist within rodent reservoirs, which are often virus specific. The family of arenaviruses are divided into two large groups, new world and old world, based upon the geographic region where they were initially isolated. A subset of arenaviruses are capable of being transmitted to humans, where they may cause viral hemorrhagic fever (VHF), a condition characterized by multiorgan system involvement, immune and vascular system dysregulation and that ultimately results in bleeding/hemorrhage and can lead to death. Licensed vaccines and therapies do not exist for many VHF causing arenaviruses. Two such viruses include Junin virus and Guanarito virus. Guinea pigs have previously used as a model to study disease pathogenesis following new world arenavirus infection. Herein we describe in detail and compare the organ system specific pathology and viral RNA distribution following separate infection in Guinea pigs, with Junin virus and Guanarito virus. This study provides valuable insight into the time course of infection, viral target tissues and similarities between two different new world arenaviruses, that will ultimately aid in development of therapies that may be effective across the spectrum of new world arenaviruses. [ABSTRACT FROM AUTHOR] |
Databáze: |
Complementary Index |
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