کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5822127 | 1557832 | 2014 | 11 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: MEK/ERK activation plays a decisive role in yellow fever virus replication: Implication as an antiviral therapeutic target MEK/ERK activation plays a decisive role in yellow fever virus replication: Implication as an antiviral therapeutic target](/preview/png/5822127.png)
- Cellular kinases can be employed as therapeutic targets to treat viral infections, by means of small molecule inhibitors.
- MEK1/2 inhibitor U0126 impairs the replication of Yellow fever virus (YFV) and other flaviviruses in vitro.
- U0126 reduces YFV genome replication, protein expression, and morphogenesis.
- In vivo replication of YFV was also reduced by the treatment with U0126.
Exploiting the inhibition of host signaling pathways aiming for discovery of potential antiflaviviral compounds is clearly a beneficial strategy for the control of life-threatening diseases caused by flaviviruses. Here we describe the antiviral activity of the MEK1/2 inhibitor U0126 against Yellow fever virus 17D vaccine strain (YFV-17D). Infection of VERO cells with YFV-17D stimulates ERK1/2 phosphorylation early during infection. Pharmacological inhibition of MEK1/2 through U0126 treatment of VERO cells blockades not only the YFV-stimulated ERK1/2 phosphorylation, but also inhibits YFV replication by â¼99%. U0126 was also effective against dengue virus (DENV-2 and -3) and Saint-Louis encephalitis virus (SLEV). Levels of NS4AB, as detected by immunofluorescence, are diminished upon treatment with the inhibitor, as well as the characteristic endoplasmic reticulum membrane invagination stimulated during the infection. Though not protective, treatment of YFV-infected, adult BALB/c mice with U0126 resulted in significant reduction of virus titers in brains. Collectively, our data suggest the potential targeting of the MEK1/2 kinase as a therapeutic tool against diseases caused by flaviviruses such as yellow fever, adverse events associated with yellow fever vaccination and dengue.
Journal: Antiviral Research - Volume 111, November 2014, Pages 82-92