Preprint Article Version 1 This version is not peer-reviewed

Analysis of MLKL, RIP1, and RIP3 Immunostaining Markers in Human Liver Tissue from Fatal Yellow Fever Cases: Insights into Necroptosis

Version 1 : Received: 20 August 2024 / Approved: 21 August 2024 / Online: 22 August 2024 (05:53:39 CEST)

How to cite: Miranda, V. D. S. C.; Falcao, L. F. M.; Lopes, J. D. C.; Fuzii, H. T.; Carvalho, M. L. G.; Filho, A. J. M.; Cruz, A. C. R.; Azevedo, R. S. S.; Sousa, J. R.; Wakimoto, M. D.; Vasconcelos, P. F. D. C.; Quaresma, J. A. S. Analysis of MLKL, RIP1, and RIP3 Immunostaining Markers in Human Liver Tissue from Fatal Yellow Fever Cases: Insights into Necroptosis. Preprints 2024, 2024081535. https://doi.org/10.20944/preprints202408.1535.v1 Miranda, V. D. S. C.; Falcao, L. F. M.; Lopes, J. D. C.; Fuzii, H. T.; Carvalho, M. L. G.; Filho, A. J. M.; Cruz, A. C. R.; Azevedo, R. S. S.; Sousa, J. R.; Wakimoto, M. D.; Vasconcelos, P. F. D. C.; Quaresma, J. A. S. Analysis of MLKL, RIP1, and RIP3 Immunostaining Markers in Human Liver Tissue from Fatal Yellow Fever Cases: Insights into Necroptosis. Preprints 2024, 2024081535. https://doi.org/10.20944/preprints202408.1535.v1

Abstract

Necroptosis is a regulated form of cell death implicated in several pathological conditions, in-cluding viral infections. In this study, we investigated the expression and correlation of necroptosis markers, MLKL, RIP1 and RIP3, in human liver tissue from fatal cases of yellow fever (YF) using immunohistochemistry (IHC). Liver samples were obtained from 21 YF-positive individuals and five flavivirus-negative controls with preserved liver parenchymal architecture. The cases un-derwent histopathological analysis, followed by tissue immunostaining with the immuno-histochemical method of streptavidin-biotin peroxidase. Using the in situ method, we evaluated the centrilobular (Z3), midzonal (Z2), periportal zone and portal tract (PT) zones of human liver parenchyma with markers for necroptosis, RIPK1, RIPK3 and MLKL. Quantitative analysis re-vealed significantly higher expression of MLKL, RIP1 and RIP3 in the liver parenchyma of YF cases compared to controls in different zones (Z3, Z2, Z1) and portal tracts (PT) of the liver, especially in zone 2. Immunostaining confirmed the localization of MLKL, RIP1 and RIP3 in hepatocytes and inflammatory infiltrates, highlighting their involvement in the pathogenesis of YF. Pearson's correlation analysis demonstrated significant correlations between necroptosis markers which indicate their coordinated regulation during YF-induced liver injury.

Keywords

Yellow Fever; Necroptosis; liver parenchyma

Subject

Medicine and Pharmacology, Tropical Medicine

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