Next Article in Journal
Full Genome Sequencing Reveals New Southern African Territories Genotypes Bringing Us Closer to Understanding True Variability of Foot-and-Mouth Disease Virus in Africa
Previous Article in Journal
Counteracting Akt Activation by HIV Protease Inhibitors in Monocytes/Macrophages
Article Menu
Issue 4 (April) cover image

Export Article

Open AccessArticle
Viruses 2018, 10(4), 191; https://doi.org/10.3390/v10040191

Combination Kinase Inhibitor Treatment Suppresses Rift Valley Fever Virus Replication

1
National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, VA 20110, USA
2
Center for Applied Proteomics and Molecular Medicine, School of Systems Biology, George Mason University, Manassas, VA 20110, USA
*
Author to whom correspondence should be addressed.
Received: 17 March 2018 / Revised: 31 March 2018 / Accepted: 10 April 2018 / Published: 13 April 2018
(This article belongs to the Section Antivirals & Vaccines)
View Full-Text   |   Download PDF [5105 KB, uploaded 3 May 2018]   |  

Abstract

Viruses must parasitize host cell translational machinery in order to make proteins for viral progeny. In this study, we sought to use this signal transduction conduit against them by inhibiting multiple kinases that influence translation. Previous work indicated that several kinases involved in translation, including p70 S6K, p90RSK, ERK, and p38 MAPK, are phosphorylated following Rift Valley fever virus (RVFV) infection. Furthermore, inhibiting p70 S6K through treatment with the FDA approved drug rapamycin prevents RVFV pathogenesis in a mouse model of infection. We hypothesized that inhibiting either p70 S6K, p90RSK, or p90RSK’s upstream kinases, ERK and p38 MAPK, would decrease translation and subsequent viral replication. Treatment with the p70 S6K inhibitor PF-4708671 resulted in decreased phosphorylation of translational proteins and reduced RVFV titers. In contrast, treatment with the p90RSK inhibitor BI-D1870, p38MAPK inhibitor SB203580, or the ERK inhibitor PD0325901 alone had minimal influence on RVFV titers. The combination of PF-4708671 and BI-D1870 treatment resulted in robust inhibition of RVFV replication. Likewise, a synergistic inhibition of RVFV replication was observed with p38MAPK inhibitor SB203580 or the ERK inhibitor PD0325901 combined with rapamycin treatment. These findings serve as a proof of concept regarding combination kinase inhibitor treatment for RVFV infection. View Full-Text
Keywords: Rift Valley fever virus; kinase; inhibitor; p38 MAPK; ERK; p70 S6K; p90RSK; mTOR; rapamycin; translation Rift Valley fever virus; kinase; inhibitor; p38 MAPK; ERK; p70 S6K; p90RSK; mTOR; rapamycin; translation
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Bell, T.M.; Espina, V.; Lundberg, L.; Pinkham, C.; Brahms, A.; Carey, B.D.; Lin, S.-C.; Dahal, B.; Woodson, C.; de la Fuente, C.; Liotta, L.A.; Bailey, C.L.; Kehn-Hall, K. Combination Kinase Inhibitor Treatment Suppresses Rift Valley Fever Virus Replication. Viruses 2018, 10, 191.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Viruses EISSN 1999-4915 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top