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Ebola virus entry requires the cholesterol transporter Niemann–Pick C1

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  • Jan E. Carette

    (Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
    Present addresses: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94304, USA (J.E.C.); Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands (G.O., T.R.B.).)

  • Matthijs Raaben

    (Harvard Medical School, Boston, Massachusetts 02115, USA)

  • Anthony C. Wong

    (Albert Einstein College of Medicine, Bronx, New York 10461, USA)

  • Andrew S. Herbert

    (US Army Medical Research Institute of Infectious Diseases, 1425 Porter St, Fort Detrick, Maryland 21702-5011, USA)

  • Gregor Obernosterer

    (Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
    Present addresses: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94304, USA (J.E.C.); Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands (G.O., T.R.B.).)

  • Nirupama Mulherkar

    (Albert Einstein College of Medicine, Bronx, New York 10461, USA)

  • Ana I. Kuehne

    (US Army Medical Research Institute of Infectious Diseases, 1425 Porter St, Fort Detrick, Maryland 21702-5011, USA)

  • Philip J. Kranzusch

    (Harvard Medical School, Boston, Massachusetts 02115, USA)

  • April M. Griffin

    (Harvard Medical School, Boston, Massachusetts 02115, USA)

  • Gordon Ruthel

    (US Army Medical Research Institute of Infectious Diseases, 1425 Porter St, Fort Detrick, Maryland 21702-5011, USA)

  • Paola Dal Cin

    (Center for Advanced Molecular Diagnostics, Shapiro 5-058, 70 Francis Street, Boston, Massachusetts 02115, USA)

  • John M. Dye

    (US Army Medical Research Institute of Infectious Diseases, 1425 Porter St, Fort Detrick, Maryland 21702-5011, USA)

  • Sean P. Whelan

    (Harvard Medical School, Boston, Massachusetts 02115, USA)

  • Kartik Chandran

    (Albert Einstein College of Medicine, Bronx, New York 10461, USA)

  • Thijn R. Brummelkamp

    (Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
    Present addresses: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94304, USA (J.E.C.); Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands (G.O., T.R.B.).)

Abstract

Filovirus infectivity factors The extraordinary virulence of the Ebola and Marburg filoviruses has spurred intensive research into the molecular mechanisms by which they multiply and cause disease. Carette et al. use a genome-wide genetic screen in human cells to identify factors required for entry of Ebola virus. The screen uncovered 67 mutations disrupting all six members of the homotypic fusion and vacuole protein-sorting (HOPS) multisubunit tethering complex, which is involved in the fusion of endosomes to lysosomes, and 39 independent mutations that disrupt the endo/lysosomal cholesterol transporter protein Niemann–Pick C1 (NPC1). Côté et al. report the identification of a novel benzylpiperazine adamantane diamide-derived compound that inhibits EboV infection in cell culture, with NPC1 being the target. The unexpected role for the hereditary disease gene NPC1 in Ebola virus infection may facilitate the development of antifilovirus therapeutics.

Suggested Citation

  • Jan E. Carette & Matthijs Raaben & Anthony C. Wong & Andrew S. Herbert & Gregor Obernosterer & Nirupama Mulherkar & Ana I. Kuehne & Philip J. Kranzusch & April M. Griffin & Gordon Ruthel & Paola Dal C, 2011. "Ebola virus entry requires the cholesterol transporter Niemann–Pick C1," Nature, Nature, vol. 477(7364), pages 340-343, September.
    • Handle: RePEc:nat:nature:v:477:y:2011:i:7364:d:10.1038_nature10348
    DOI: 10.1038/nature10348
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    Cited by:

    1. Massimo Florio & Simona Gamba, 2021. "Biomed Europa: After the coronavirus, a public infrastructure to overcome the pharmaceutical oligopoly," Annals of Public and Cooperative Economics, Wiley Blackwell, vol. 92(3), pages 387-409, September.
    2. Gamba, Simona & Magazzini, Laura & Pertile, Paolo, 2021. "R&D and market size: Who benefits from orphan drug legislation?," Journal of Health Economics, Elsevier, vol. 80(C).
    3. Evelyn Fessler & Luisa Krumwiede & Lucas T. Jae, 2022. "DELE1 tracks perturbed protein import and processing in human mitochondria," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    4. Vanessa Monteil & Hyesoo Kwon & Lijo John & Cristiano Salata & Gustav Jonsson & Sabine U. Vorrink & Sofia Appelberg & Sonia Youhanna & Matheus Dyczynski & Alexandra Leopoldi & Nicole Leeb & Jennifer V, 2023. "Identification of CCZ1 as an essential lysosomal trafficking regulator in Marburg and Ebola virus infections," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    5. Iquo A. Archibong & Mfonabasi U. Inyang & Emmanuel Okon & Idongesit A. Victor, 2020. "Ebola Virus Immuno-Evasion and Cellular Dysfunctional Mechanics: A Bio-Terrorizing Agent of Zoonotic Origin," International Journal of Research and Scientific Innovation, International Journal of Research and Scientific Innovation (IJRSI), vol. 7(9), pages 324-338, September.
    6. Ilyas Khan & Sunan Li & Lihong Tao & Chong Wang & Bowei Ye & Huiyu Li & Xiaoyang Liu & Iqbal Ahmad & Wenqiang Su & Gongxun Zhong & Zhiyuan Wen & Jinliang Wang & Rong-Hong Hua & Ao Ma & Jie Liang & Xia, 2024. "Tubeimosides are pan-coronavirus and filovirus inhibitors that can block their fusion protein binding to Niemann-Pick C1," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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