Two-pore channels control Ebola virus host cell entry and are drug targets for disease treatment

Author:

Sakurai Yasuteru1,Kolokoltsov Andrey A.2,Chen Cheng-Chang3,Tidwell Michael W.4,Bauta William E.4,Klugbauer Norbert5,Grimm Christian3,Wahl-Schott Christian3,Biel Martin3,Davey Robert A.1

Affiliation:

1. Texas Biomedical Research Institute, San Antonio, TX, USA.

2. The University of Texas Medical Branch, Galveston, TX, USA.

3. Center for Integrated Protein Science Munich (CIPSM) at the Department of Pharmacy–Center for Drug Research, Ludwig-Maximilians-Universität München, Munich, Germany.

4. Southwest Research Institute, San Antonio, TX, USA.

5. Institute for Experimental and Clinical Pharmacology and Toxicology, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.

Abstract

Channeling Ebola virus entry into the cell The current outbreak of Ebola virus in West Africa highlights the need for antiviral therapies. One strategy would be to block the Ebola virus's ability to enter host cells. Cells engulf Ebola virus particles, which then traffic into the cell in structures called endosomes. Sakurai et al. now report that the Ebola virus requires calcium channels called two-pore channels (TPCs) in endosomal membranes for successful entry (see the Perspective by Falzarano and Feldmann). The Ebola virus could not enter cells lacking TPCs or cells treated with a TPC inhibitor. Blocking TPCs therapeutically allowed 50% of mice to survive an ordinarily lethal Ebola virus infection. Science , this issue p. 995 ; see also p. 947

Funder

NIH

DOD/DTRA

Ewing Halsell Foundation

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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