Format

Send to

Choose Destination
Virology. 2018 Jan 1;513:17-28. doi: 10.1016/j.virol.2017.09.028. Epub 2017 Oct 12.

Ebola virus requires phosphatidylinositol (3,5) bisphosphate production for efficient viral entry.

Author information

1
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Canada.
2
Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada.
3
Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.
4
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Canada. Electronic address: marceline.cote@uottawa.ca.

Abstract

For entry, Ebola virus (EBOV) requires the interaction of its viral glycoprotein with the cellular protein Niemann-Pick C1 (NPC1) which resides in late endosomes and lysosomes. How EBOV is trafficked and delivered to NPC1 and whether this is positively regulated during entry remain unclear. Here, we show that the PIKfyve-ArPIKfyve-Sac3 cellular complex, which is involved in the metabolism of phosphatidylinositol (3,5) bisphosphate (PtdIns(3,5)P2), is critical for EBOV infection. Although the expression of all subunits of the complex was required for efficient entry, PIKfyve kinase activity was specifically critical for entry by all pathogenic filoviruses. Inhibition of PIKfyve prevented colocalization of EBOV with NPC1 and led to virus accumulation in intracellular vesicles with characteristics of early endosomes. Importantly, genetically-encoded phosphoinositide probes revealed an increase in PtdIns(3,5)P2-positive vesicles in cells during EBOV entry. Taken together, our studies suggest that EBOV requires PtdIns(3,5)P2 production in cells to promote efficient delivery to NPC1.

KEYWORDS:

Filoviruses; Vesicular trafficking; Viral entry; Virus-cell interactions

PMID:
29031163
DOI:
10.1016/j.virol.2017.09.028
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center