Next Article in Journal
Low Temperature and Low UV Indexes Correlated with Peaks of Influenza Virus Activity in Northern Europe during 2010–2018
Next Article in Special Issue
A Lactic Acid Bacteria (LAB)-Based Vaccine Candidate for Human Norovirus
Previous Article in Journal
A Needle in A Haystack: Tracing Bivalve-Associated Viruses in High-Throughput Transcriptomic Data
Previous Article in Special Issue
The Two Prevalent Genotypes of an Emerging Infectious Disease, Deformed Wing Virus, Cause Equally Low Pupal Mortality and Equally High Wing Deformities in Host Honey Bees
Open AccessArticle

A Diacylglycerol Kinase Inhibitor, R-59-022, Blocks Filovirus Internalization in Host Cells

1
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada
2
Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, ON K1H 8M5, Canada
3
Centre for Infection, Immunity and Inflammation, University of Ottawa, Ottawa, ON K1H 8M5, Canada
4
Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, Canada
5
Department of Medical Microbiology, University of Manitoba, Winnipeg, MB R3E 0J9, Canada
*
Author to whom correspondence should be addressed.
Viruses 2019, 11(3), 206; https://doi.org/10.3390/v11030206
Received: 12 February 2019 / Revised: 25 February 2019 / Accepted: 26 February 2019 / Published: 1 March 2019
(This article belongs to the Special Issue Emerging Viruses)
Filoviruses, such as Ebola virus (EBOV) and Marburg virus, are causative agents of unpredictable outbreaks of severe hemorrhagic fevers in humans and non-human primates. For infection, filoviral particles need to be internalized and delivered to intracellular vesicles containing cathepsin proteases and the viral receptor Niemann-Pick C1. Previous studies have shown that EBOV triggers macropinocytosis of the viral particles in a glycoprotein (GP)-dependent manner, but the molecular events required for filovirus internalization remain mostly unknown. Here we report that the diacylglycerol kinase inhibitor, R-59-022, blocks EBOV GP-mediated entry into Vero cells and bone marrow-derived macrophages. Investigation of the mode of action of the inhibitor revealed that it blocked an early step in entry, more specifically, the internalization of the viral particles via macropinocytosis. Finally, R-59-022 blocked viral entry mediated by a panel of pathogenic filovirus GPs and inhibited growth of replicative Ebola virus. Taken together, our studies suggest that R-59-022 could be used as a tool to investigate macropinocytic uptake of filoviruses and could be a starting point for the development of pan-filoviral therapeutics. View Full-Text
Keywords: Ebola virus; Marburg virus; filoviruses; viral entry; macropinocytosis; diacylglycerol kinase Ebola virus; Marburg virus; filoviruses; viral entry; macropinocytosis; diacylglycerol kinase
Show Figures

Figure 1

MDPI and ACS Style

Stewart, C.M.; Dorion, S.S.; Ottenbrite, M.A.F.; LeBlond, N.D.; Smith, T.K.T.; Qiu, S.; Fullerton, M.D.; Kobasa, D.; Côté, M. A Diacylglycerol Kinase Inhibitor, R-59-022, Blocks Filovirus Internalization in Host Cells. Viruses 2019, 11, 206. https://doi.org/10.3390/v11030206

AMA Style

Stewart CM, Dorion SS, Ottenbrite MAF, LeBlond ND, Smith TKT, Qiu S, Fullerton MD, Kobasa D, Côté M. A Diacylglycerol Kinase Inhibitor, R-59-022, Blocks Filovirus Internalization in Host Cells. Viruses. 2019; 11(3):206. https://doi.org/10.3390/v11030206

Chicago/Turabian Style

Stewart, Corina M.; Dorion, Stephanie S.; Ottenbrite, Marie A.F.; LeBlond, Nicholas D.; Smith, Tyler K.T.; Qiu, Shirley; Fullerton, Morgan D.; Kobasa, Darwyn; Côté, Marceline. 2019. "A Diacylglycerol Kinase Inhibitor, R-59-022, Blocks Filovirus Internalization in Host Cells" Viruses 11, no. 3: 206. https://doi.org/10.3390/v11030206

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

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop