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Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein

Author

Listed:
  • Kasia Hrecka

    (Case School of Medicine
    Cold Spring Harbor Laboratory)

  • Caili Hao

    (Case School of Medicine)

  • Magda Gierszewska

    (Cold Spring Harbor Laboratory)

  • Selene K. Swanson

    (Stowers Institute for Medical Research)

  • Malgorzata Kesik-Brodacka

    (Case School of Medicine
    Present addresses: Department of Pathology, New York School of Medicine, New York, New York 10016, USA (S.S.); Institute of Biotechnology and Antibiotics, Warsaw 02-516, Poland (M.K.-B.).)

  • Smita Srivastava

    (Cold Spring Harbor Laboratory
    Present addresses: Department of Pathology, New York School of Medicine, New York, New York 10016, USA (S.S.); Institute of Biotechnology and Antibiotics, Warsaw 02-516, Poland (M.K.-B.).)

  • Laurence Florens

    (Stowers Institute for Medical Research)

  • Michael P. Washburn

    (Stowers Institute for Medical Research
    University of Kansas Medical Center)

  • Jacek Skowronski

    (Case School of Medicine
    Cold Spring Harbor Laboratory)

Abstract

How macrophages avoid HIV-1 infection HIV-1 is unable to replicate efficiently in dendritic cells, the antigen-presenting tissue cells that function in both innate and adaptive immunity. Other primate lentiviruses, including HIV-2 and some simian immunodeficiency viruses, express a protein called Vpx that is able to overcome the block to replication. Two groups now report the identification of the restriction factor in dendritic cells and macrophages that is overcome by Vpx. Vpx is found to induce degradation of the protein SAMHD1. Mutations in SAMHD1 cause Aicardi–Goutières syndrome, a disorder characterized by inappropriate activation of the immune system. Knockdown of SAMHD1 increases HIV-1 replication in dendritic cells, which could be important for generating appropriate immune responses to the virus.

Suggested Citation

  • Kasia Hrecka & Caili Hao & Magda Gierszewska & Selene K. Swanson & Malgorzata Kesik-Brodacka & Smita Srivastava & Laurence Florens & Michael P. Washburn & Jacek Skowronski, 2011. "Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein," Nature, Nature, vol. 474(7353), pages 658-661, June.
    • Handle: RePEc:nat:nature:v:474:y:2011:i:7353:d:10.1038_nature10195
    DOI: 10.1038/nature10195
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    Cited by:

    1. Priya Kapoor-Vazirani & Sandip K. Rath & Xu Liu & Zhen Shu & Nicole E. Bowen & Yitong Chen & Ramona Haji-Seyed-Javadi & Waaqo Daddacha & Elizabeth V. Minten & Diana Danelia & Daniela Farchi & Duc M. D, 2022. "SAMHD1 deacetylation by SIRT1 promotes DNA end resection by facilitating DNA binding at double-strand breaks," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Oliver J. Acton & Devon Sheppard & Simone Kunzelmann & Sarah J. Caswell & Andrea Nans & Ailidh J. O. Burgess & Geoff Kelly & Elizabeth R. Morris & Peter B. Rosenthal & Ian A. Taylor, 2024. "Platform-directed allostery and quaternary structure dynamics of SAMHD1 catalysis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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