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Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein

Author

Listed:
  • Ann M. Sheehy

    (University of Pennsylvania School of Medicine)

  • Nathan C. Gaddis

    (University of Pennsylvania School of Medicine)

  • Jonathan D. Choi

    (The Children's Hospital of Philadelphia)

  • Michael H. Malim

    (University of Pennsylvania School of Medicine
    Guy's, King's and St Thomas' School of Medicine, King's College London)

Abstract

Viruses have developed diverse non-immune strategies to counteract host-mediated mechanisms that confer resistance to infection. The Vif (virion infectivity factor) proteins are encoded by primate immunodeficiency viruses, most notably human immunodeficiency virus-1 (HIV-1). These proteins are potent regulators of virus infection and replication and are consequently essential for pathogenic infections in vivo1,2,3,4,5,6. HIV-1 Vif seems to be required during the late stages of virus production3,6 for the suppression of an innate antiviral phenotype that resides in human T lymphocytes7,8. Thus, in the absence of Vif, expression of this phenotype renders progeny virions non-infectious. Here, we describe a unique cellular gene, CEM15, whose transient or stable expression in cells that do not normally express CEM15 recreates this phenotype, but whose antiviral action is overcome by the presence of Vif. Because the Vif:CEM15 regulatory circuit is critical for HIV-1 replication, perturbing the circuit may be a promising target for future HIV/AIDS therapies.

Suggested Citation

  • Ann M. Sheehy & Nathan C. Gaddis & Jonathan D. Choi & Michael H. Malim, 2002. "Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein," Nature, Nature, vol. 418(6898), pages 646-650, August.
    • Handle: RePEc:nat:nature:v:418:y:2002:i:6898:d:10.1038_nature00939
    DOI: 10.1038/nature00939
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    Cited by:

    1. Diako Ebrahimi & Hamid Alinejad-Rokny & Miles P Davenport, 2014. "Insights into the Motif Preference of APOBEC3 Enzymes," PLOS ONE, Public Library of Science, vol. 9(1), pages 1-9, January.
    2. Hannah O. Ajoge & Tyler M. Renner & Kasandra Bélanger & Matthew Greig & Samar Dankar & Hinissan P. Kohio & Macon D. Coleman & Emmanuel Ndashimye & Eric J. Arts & Marc-André Langlois & Stephen D. Barr, 2023. "Antiretroviral APOBEC3 cytidine deaminases alter HIV-1 provirus integration site profiles," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Hanjing Yang & Kyumin Kim & Shuxing Li & Josue Pacheco & Xiaojiang S. Chen, 2022. "Structural basis of sequence-specific RNA recognition by the antiviral factor APOBEC3G," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    4. Vanessa B Soros & Wes Yonemoto & Warner C Greene, 2007. "Newly Synthesized APOBEC3G Is Incorporated into HIV Virions, Inhibited by HIV RNA, and Subsequently Activated by RNase H," PLOS Pathogens, Public Library of Science, vol. 3(2), pages 1-16, February.
    5. Jing Ma & Xiaoyu Li & Jian Xu & Quan Zhang & Zhenlong Liu & Pingping Jia & Jinming Zhou & Fei Guo & Xuefu You & Liyan Yu & Lixun Zhao & Jiandong Jiang & Shan Cen, 2013. "The Roles of APOBEC3G Complexes in the Incorporation of APOBEC3G into HIV-1," PLOS ONE, Public Library of Science, vol. 8(10), pages 1-9, October.
    6. Iraj Hosseini & Feilim Mac Gabhann, 2012. "Multi-Scale Modeling of HIV Infection in vitro and APOBEC3G-Based Anti-Retroviral Therapy," PLOS Computational Biology, Public Library of Science, vol. 8(2), pages 1-17, February.
    7. Atanu Maiti & Adam K. Hedger & Wazo Myint & Vanivilasini Balachandran & Jonathan K. Watts & Celia A. Schiffer & Hiroshi Matsuo, 2022. "Structure of the catalytically active APOBEC3G bound to a DNA oligonucleotide inhibitor reveals tetrahedral geometry of the transition state," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    8. Fumiaki Ito & Ana L. Alvarez-Cabrera & Kyumin Kim & Z. Hong Zhou & Xiaojiang S. Chen, 2023. "Structural basis of HIV-1 Vif-mediated E3 ligase targeting of host APOBEC3H," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    9. Joseph Hiatt & Judd F. Hultquist & Michael J. McGregor & Mehdi Bouhaddou & Ryan T. Leenay & Lacy M. Simons & Janet M. Young & Paige Haas & Theodore L. Roth & Victoria Tobin & Jason A. Wojcechowskyj & , 2022. "A functional map of HIV-host interactions in primary human T cells," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    10. Takahide Kouno & Satoshi Shibata & Megumi Shigematsu & Jaekyung Hyun & Tae Gyun Kim & Hiroshi Matsuo & Matthias Wolf, 2023. "Structural insights into RNA bridging between HIV-1 Vif and antiviral factor APOBEC3G," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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