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Ubertino

09/15/14 10:26 AM

#98842 RE: Ubertino #98781

Ebola virus entry requires the cholesterol transporter Niemann-Pick C1

Jan E. Carette,1,2,* Matthijs Raaben,3,* Anthony C. Wong,4,* Andrew S. Herbert,5 Gregor Obernosterer,1,6 Nirupama Mulherkar,4 Ana I. Kuehne,5 Philip J. Kranzusch,3 April M. Griffin,3 Gordon Ruthel,5 Paola Dal Cin,7 John M. Dye,5,§ Sean P. Whelan,3,§ Kartik Chandran,4,§ and Thijn R. Brummelkamp1,6,§

1Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge 02142 MA, USA
3Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115
4Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
5U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St., Fort Detrick, Maryland 21702-5011
7Center for Advanced Molecular Diagnostics, Shapiro 5-058, 70 Francis Street, Boston, MA 02115
Correspondence to Thijn R. Brummelkamp1,5, Email: ln.ikn@pmaklemmurb.t, Kartik Chandran4, Email: ude.uy.nietsnie@nardnahc.kitrak,. Sean P. Whelan3, Email: ude.dravrah.smh@nalehw_naes, John M. Dye6, Email: lim.ymra.su@1eyD.M.nhoJ
2Current address: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94304, USA.
6Current address: Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
*These authors contributed equally to the study.
§These authors contributed equally to the study.

We show that membrane fusion mediated by filovirus glycoproteins and viral escape from the vesicular compartment require the NPC1 protein, independent of its known function in cholesterol transport. Our findings uncover unique features of the entry pathway used by filoviruses and indicate potential antiviral strategies to combat these deadly agents.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175325/