Neutral sphingomyelinase 2 is required for HIV-1 maturation
Year: 2023
Type: article
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.
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Funders: Johns Hopkins University, Wellcome Trust, Diamond Light Source, Frederick National Laboratory for Cancer Research, University of Oxford, Chinese Academy of Medical Sciences, National Institutes of Health, Directorate for Biological Sciences, Medical Research Council, Biotechnology and Biological Sciences Research Council, National Institute on Aging, National Institute of Mental Health, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, H2020 European Research Council
Awards: Molecular choreography of bacterial chemotaxis signalling, G1464318188, G1547711591, G1807484332, G2154807241, Exosomes:From biogenesis and secretion to the early pathogenesis of Alzheimer's disease, G2609650503, G2845260842, Pittsburgh Center for HIV Protein Interactions (PCHPI), G339059223, Assembly and Dynamics of Bacterial Chemosensory Signaling Arrays, Regulation of Exosome Secretion as a novel therapeutic approach for Alzheimer's Disease, G5413119319, G563806405, G5927648607, Molecular mechanisms of HIV-1 restriction by capsid-sensing host cell proteins, G7481841952, G8732200567, G9000045202, G9000258633, A Sphingomyelin Hydrolase Regulates the Late Stages of HIV Assembly and Budding, The Johns Hopkins Center for AIDS Research (JHU CFAR), Pittsburgh Center for HIV Protein Interactions (PCHPI), JHU Center for the Advancement of HIV Neurotherapeutics (JHU CAHN)
OpenAlex ID: W4383294872