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Cellular visualization of macrophage pyroptosis and interleukin-1? release in a
viral hemorrhagic infection in zebrafish larvae
#MMPMID25100833
Varela M
; Romero A
; Dios S
; van der Vaart M
; Figueras A
; Meijer AH
; Novoa B
J Virol
2014[Oct]; 88
(20
): 12026-40
PMID25100833
show ga
Hemorrhagic viral diseases are distributed worldwide with important pathogens,
such as dengue virus or hantaviruses. The lack of adequate in vivo infection
models has limited the research on viral pathogenesis and the current
understanding of the underlying infection mechanisms. Although hemorrhages have
been associated with the infection of endothelial cells, other cellular types
could be the main targets for hemorrhagic viruses. Our objective was to take
advantage of the use of zebrafish larvae in the study of viral hemorrhagic
diseases, focusing on the interaction between viruses and host cells. Cellular
processes, such as transendothelial migration of leukocytes, virus-induced
pyroptosis of macrophages. and interleukin-1? (Il-1?) release, could be observed
in individual cells, providing a deeper knowledge of the immune mechanisms
implicated in the disease. Furthermore, the application of these techniques to
other pathogens will improve the current knowledge of host-pathogen interactions
and increase the potential for the discovery of new therapeutic targets.
Importance: Pathogenic mechanisms of hemorrhagic viruses are diverse, and most of
the research regarding interactions between viruses and host cells has been
performed in cell lines that might not be major targets during natural
infections. Thus, viral pathogenesis research has been limited because of the
lack of adequate in vivo infection models. The understanding of the relative
pathogenic roles of the viral agent and the host response to the infection is
crucial. This will be facilitated by the establishment of in vivo infection
models using organisms such as zebrafish, which allows the study of the diseases
in the context of a complete individual. The use of this animal model with other
pathogens could improve the current knowledge on host-pathogen interactions and
increase the potential for the discovery of new therapeutic targets against
diverse viral diseases.