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Neutral sphingomyelinase 2 is required for HIV-1 maturation

  1. Author:
    Waheed, Abdul A
    Zhu, Yanan [ORCID]
    Agostino, Eva
    Naing, Lwar [ORCID]
    Hikichi, Yuta [ORCID]
    Soheilian,Ferri
    Yoo, Seung-Wan
    Song, Yun [ORCID]
    Zhang, Peijun [ORCID]
    Slusher, Barbara S [ORCID]
    Haughey, Norman J
    Freed, Eric O

  2. Author Address

    Virus-Cell Interaction Section, HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702., Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom., Electron Microscopy Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702., Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287., Electron Bio-Imaging Centre, Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE, United Kingdom., Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford OX3 7BN, United Kingdom., Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21287., Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287.,
    1. Year: 2023
    2. Date: Jul 11
    3. Epub Date: 2023 07 05
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 120
    2. 28
    3. Pages: e2219475120
  4. Type of Article: Article
  5. Article Number: e2219475120
  1. Abstract:

    HIV-1 assembly occurs at the inner leaflet of the plasma membrane (PM) in highly ordered membrane microdomains. The size and stability of membrane microdomains is regulated by activity of the sphingomyelin hydrolase neutral sphingomyelinase 2 (nSMase2) that is localized primarily to the inner leaflet of the PM. In this study, we demonstrate that pharmacological inhibition or depletion of nSMase2 in HIV-1-producer cells results in a block in the processing of the major viral structural polyprotein Gag and the production of morphologically aberrant, immature HIV-1 particles with severely impaired infectivity. We find that disruption of nSMase2 also severely inhibits the maturation and infectivity of other primate lentiviruses HIV-2 and simian immunodeficiency virus, has a modest or no effect on nonprimate lentiviruses equine infectious anemia virus and feline immunodeficiency virus, and has no effect on the gammaretrovirus murine leukemia virus. These studies demonstrate a key role for nSMase2 in HIV-1 particle morphogenesis and maturation.

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External Sources

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  2. DOI: 10.1073/pnas.2219475120
  3. PMID: 37406093

Library Notes

  1. Fiscal Year: FY2022-2023
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