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Research Project: Intervention Strategies to Prevent and Control Crimean-Congo Hemorrhagic Fever (CCHF)

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Title: An atlas of gross and histologic lesions and immunohistochemical immunoreactivity during the temporal progression of aerosolized Lassa virus induced hemorrhagic fever in cynomolgus macaques

Author
item Hensley, Lisa
item BOHLER, FORREST - National Institutes Of Health (NIH)
item CASHMAN, KATHLEEN - Us Army Medical Research Institute Of Infectious Diseases
item WILKINSON, ERIC - Us Army Medical Research Institute Of Infectious Diseases
item JONSON, JOSHUA - Us Army Medical Research Institute Of Infectious Diseases
item ROSENKE, KYLE - National Institutes Of Health (NIH)
item SHAMBLIN, JOSH - Us Army Medical Research Institute Of Infectious Diseases
item HONKO, ANNA - Us Army Medical Research Institute Of Infectious Diseases
item SHAIA, CARL - National Institutes Of Health (NIH)

Submitted to: Frontiers in Cellular and Infection Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/15/2024
Publication Date: 2/9/2024
Citation: Hensley, L.E., Bohler, F., Cashman, K., Wilkinson, E., Jonson, J.C., Rosenke, K., Shamblin, J., Honko, A., Shaia, C. 2024. An atlas of gross and histologic lesions and immunohistochemical immunoreactivity during the temporal progression of aerosolized Lassa virus induced hemorrhagic fever in cynomolgus macaques. Frontiers in Cellular and Infection Microbiology. 14. https://doi.org/10.3389/fcimb.2024.1341891.
DOI: https://doi.org/10.3389/fcimb.2024.1341891

Interpretive Summary: This paper describes the disease progression of Lassa Fever virus, a hemorrhagic fever virus. There are an estimated 100000 - 300000 cases each year and there are currently no approved vaccines or therapeutics. The characterization of the disease progression will help scientists identify treatment strategies and will also provide data to help regulatory agencies review preclinical data.

Technical Abstract: Lassa virus (LASV) causes an acute multisystemic hemorrhagic fever in humans known as Lassa fever, which is endemic in several African countries. This manuscript focuses on the progression of disease in cynomolgus macaques challenged with aerosolized LASV and serially sampled for the development and progression of gross and histopathologic lesions. Gross lesions were first noted in tissues on day 6 and persisted throughout day 12. Viremia and histologic lesions were first noted on day 6 commencing with the pulmonary system and hemolymphatic system and progressing at later time points to include all systems. Immunoreactivity to LASV antigen was first observed in the lungs of one macaque on day 3 and appeared localized to macrophages with an increase at later time points to include immunoreactivity in all organ systems. Additionally, this manuscript will serve as a detailed atlas of histopathologic lesions and disease progression for comparison to other animal models of aerosolized Arenaviral disease.