Skip NavigationSkip to Content
Return Return to Search Results

A stable immature lattice packages IP6 for HIV capsid maturation

  1. Author:
    Mallery, Donna L.
    Kleinpeter,Alex
    Renner, Nadine
    Faysal, K. M. Rifat
    Novikova, Mariia
    Kiss, Leo
    Wilson, Miranda S. C.
    Ahsan, Bilal
    Ke, Zunlong
    Briggs, John A. G.
    Saiardi, Adolfo
    Bocking, Till
    Freed,Eric
    James, Leo C.

  2. Author Address

    MRC Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England.NCI, Virus Cell Interact Sect, HIV Dynam & Replicat Program, Ctr Canc Res, Frederick, MD 21702 USA.UNSW Sydney, Sch Med Sci, EMBL Australia Node Single Mol Sci, Sydney, NSW, Australia.UNSW Sydney, ARC Ctr Excellence Adv Mol Imaging, Sch Med Sci, Sydney, NSW, Australia.UCL, MRC Lab Mol Cell Biol, London, England.
    1. Year: 2021
    2. Date: Mar 10
  2. Journal: Science Advances
  3. Amer Assoc Advancement Science
    1. 7
    2. 11
  5. Type of Article: Article
  6. Article Number: ARTN eabe4716
  7. ISSN: 2375-2548
  1. Abstract:

    HIV virion assembly begins with the construction of an immature lattice consisting of Gag hexamers. Upon virion release, protease-mediated Gag cleavage leads to a maturation event in which the immature lattice disassembles and the mature capsid assembles. The cellular metabolite inositiol hexakisphosphate (IP6) and maturation inhibitors (MIs) both bind and stabilize immature Gag hexamers, but whereas IP6 promotes virus maturation, Mls inhibit it. Here we show that HIV is evolutionarily constrained to maintain an immature lattice stability that ensures IP6 packaging without preventing maturation. Replication-deficient mutant viruses with reduced IP6 recruitment display increased infectivity upon treatment with the MI PF46396 (PF96) or the acquisition of second-site compensatory mutations. Both PF96 and second-site mutations stabilise the immature lattice and restore IP6 incorporation, suggesting that immature lattice stability and IP6 binding are interdependent. This IP6 dependence suggests that modifying Mls to compete with IP6 for Gag hexamer binding could substantially improve MI antiviral potency.

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1126/sciadv.abe4716
  3. PMID: 33692109
  4. PMCID: PMC7946374
  5. View record in Web of Science®
  6. WOS: 000628616300017

Library Notes

  1. Fiscal Year: FY2020-2021
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel