DHEA inhibits measles virus through a mechanism independent of its ability to modulate the Raf/MEK/ERK signaling pathway

Aim: Despite the existence of an effective vaccine, measles infection is still frequent in many developing countries with reduced health infrastructure, and it is one of the major causes of child death globally. In the past decade numerous outbreaks have occurred in developed countries, giving a fre...

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Detalles Bibliográficos
Autores principales: Torres, N.I., Castilla, V., Wachsman, M.
Formato: JOUR
Materias:
anisomycin
antiviral agents
DHEA
measles virus
Raf/MEK/ERK signaling pathway
UO126
1,4 diamino 1,4 bis(2 aminophenylthio) 2,3 dicyanobutadiene
mitogen activated protein kinase 1
mitogen activated protein kinase 3
prasterone
Raf protein
ribavirin
virus antigen
adsorption
animal cell
antiviral activity
article
concentration response
drug cytotoxicity
drug mechanism
enzyme activation
enzyme phosphorylation
immunofluorescence
Measles virus
nonhuman
priority journal
signal transduction
Vero cell
virus inhibition
virus pathogenesis
virus replication
Western blotting
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_17460794_v7_n11_p1115_Torres
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario:Aim: Despite the existence of an effective vaccine, measles infection is still frequent in many developing countries with reduced health infrastructure, and it is one of the major causes of child death globally. In the past decade numerous outbreaks have occurred in developed countries, giving a fresh impetus to antiviral research against measles virus. The aim of this study was to investigate the antiviral activity of the natural steroid hormone DHEA against measles virus and the role of the Raf/MEK/ERK signaling pathway in viral multiplication and DHEA's antiviral activity. Materials & methods: The antiviral activity of DHEA and two ERK modulators, UO126 and anisomycin, was determined using a virus yield reduction assay. Furthermore, we studied DHEA's virucidal activity and the viral multiplication step affected by the compound. The effect of virus infection on the Raf/MEK/ERK pathway and the activity of those compounds against measles virus spread and induced cytopathic effect were studied using western blot and indirect immunofluorescence. Results & conclusion: We found that DHEA and UO126 are active against measles virus and that they are able to diminish virus-induced cytopathic effects. Also, our study showed that early events in the viral multiplication cycle trigger ERK activation, suggesting that DHEA, a Raf/MEK/ERK modulator, may not exert its antiviral activity through the modulation of this pathway. Our results may provide a first step in the development of new antiviral agents against measles virus. © 2012 Future Medicine Ltd.

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