Factors Involved in the Apoptotic Cell Death Mechanism in Yellow Fever Hepatitis

Author:

da Costa Lopes JefersonORCID,Falcão Luiz Fábio MagnoORCID,Martins Filho Arnaldo JorgeORCID,Carvalho Marcos Luiz GaiaORCID,Mendes Caio Cesar Henriques,Olímpio Fábio AlvesORCID,do Socorro Cabral Miranda VanessaORCID,dos Santos Lais Carneiro,Chiang Jannifer OliveiraORCID,Cruz Ana Cecilia RibeiroORCID,Galúcio Vanessa Costa Alves,do Socorro da Silva Azevedo RaimundaORCID,Martins Lívia Caricio,Duarte Maria Irma SeixasORCID,de Sousa Jorge Rodrigues,da Costa Vasconcelos Pedro FernandoORCID,Quaresma Juarez Antônio SimõesORCID

Abstract

Yellow fever (YF), a non-contagious infectious disease, is endemic or enzootic to the tropical regions of the Americas and Africa. Periodic outbreaks or epidemics have a significant impact on public health. Programmed cell death, or apoptosis, is generally characterised by distinct morphological changes and energy-dependent biochemical pathways. In this study, we performed immunohistochemistry analysis to identify and quantify proteases and protein targets involved in the cascade that triggers apoptosis in YF virus (YFV)-infected human hepatocytes. Liver tissue samples were collected from 26 individuals, among whom 21 were diagnosed as YF-positive, and five were flavivirus-negative and died due to other causes. The histopathological alterations in YFV-positive cases were characterised by the presence of apoptotic bodies, steatosis, cellular swelling, and extensive necrosis and haemorrhage in the hepatic lobules. Additionally, we observed an abundance of inflammatory infiltrates in the portal tract. The expression of various apoptotic markers in the hepatic parenchyma, including CASPASE 3, CASPASE 8, BAX, FAS, FASL, GRANZYME B, and SURVIVIN, differed between YFV-positive cases and controls. Collectively, this study confirmed the complexity of YFV infection-induced apoptosis in situ. However, our data suggest that apoptosis in liver parenchyma lesions may significantly contribute to the pathogenesis of fatal YF in humans.

Funder

National Council for Scientific and Technological Development

Federal University of Para

Publisher

MDPI AG

Subject

Virology,Infectious Diseases

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Viral etiologies of acute liver failure;World Journal of Virology;2024-09-25

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