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

Viruses

Luiz Fábio Magno Falcão¹  Vanessa Costa Alves Galúcio¹  Caio Cesar Henriques Mendes¹  Juarez Antônio Simões Quaresma¹  Lais Carneiro dos Santos²  Vanessa do Socorro Cabral Miranda²  Raimunda do Socorro da Silva Azevedo²  Jannifer Oliveira Chiang²  Ana Cecilia Ribeiro Cruz²  Arnaldo Jorge Martins Filho²  Pedro Fernando da Costa Vasconcelos²  Jeferson da Costa Lopes²  Marcos Luiz Gaia Carvalho²  Jorge Rodrigues de Sousa²  Lívia Caricio Martins²  Maria Irma Seixas Duarte³  Fábio Alves Olímpio⁴ 

[1] Department of Pathology, State University of Para, Belem 66050-540, Brazil;Evandro Chagas Institut, Ministry of Health, Ananindeua 67015-120, Brazil;Schhol of Medicine, Sao Paulo University, Sao Paulo 05508-070, Brazil;Tripical Medicine Unit, Federal University of Para, Belem 66075-110, Brazil;

关键词: cell death;    flavivirus;    pathogenesis;    apoptosis;    arbovirus;   

DOI  :  10.3390/v14061204

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown