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Cellular IP6 Levels Limit HIV Production while Viruses that Cannot Efficiently Package IP6 Are Attenuated for Infection and Replication

  1. Author:
    Mallery, Donna L
    Faysal, K M Rifat
    Kleinpeter,Alex
    Wilson, Miranda S C
    Vaysburd, Marina
    Fletcher, Adam J
    Novikova, Mariia
    Böcking, Till
    Freed,Eric
    Saiardi, Adolfo
    James, Leo C

  2. Author Address

    MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK., EMBL Australia Node in Single Molecule Science and ARC Centre of Excellence in Advanced Molecular Imaging, School of Medical Sciences, UNSW Sydney, Sydney NSW, Australia., Virus-Cell Interaction Section, HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702-1201, USA., MRC Laboratory for Molecular Cell Biology, University College London, London, UK., MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Dundee, UK., MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK. Electronic address: lcj@mrc-lmb.cam.ac.uk.,
    1. Year: 2019
    2. Date: Dec 17
  2. Journal: Cell reports
    1. 29
    2. 12
    3. Pages: 3983-3996.e4
  4. Type of Article: Article
  5. ISSN: 2211-1247
  1. Abstract:

    HIV-1 hijacks host proteins to promote infection. Here we show that HIV is also dependent upon the host metabolite inositol hexakisphosphate (IP6) for viral production and primary cell replication. HIV-1 recruits IP6 into virions using two lysine rings in its immature hexamers. Mutation of either ring inhibits IP6 packaging and reduces viral production. Loss of IP6 also results in virions with highly unstable capsids, leading to a profound loss of reverse transcription and cell infection. Replacement of one ring with a hydrophobic isoleucine core restores viral production, but IP6 incorporation and infection remain impaired, consistent with an independent role for IP6 in stable capsid assembly. Genetic knockout of biosynthetic kinases IPMK and IPPK reveals that cellular IP6 availability limits the production of diverse lentiviruses, but in the absence of IP6, HIV-1 packages IP5 without loss of infectivity. Together, these data suggest that IP6 is a critical cofactor for HIV-1 replication. Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.celrep.2019.11.050
  3. PMID: 31851928
  4. View record in Web of Science®
  5. WOS: 000503201800019
  6. PII : S2211-1247(19)31532-3

Library Notes

  1. Fiscal Year: FY2019-2020
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