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TitleNeutral sphingomyelinase 2 is required for HIV-1 maturation.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 120, Issue 28, Page e2219475120, Year 2023
Publish dateJul 11, 2023
AuthorsAbdul A Waheed / Yanan Zhu / Eva Agostino / Lwar Naing / Yuta Hikichi / Ferri Soheilian / Seung-Wan Yoo / Yun Song / Peijun Zhang / Barbara S Slusher / Norman J Haughey / Eric O Freed /
PubMed AbstractHIV-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 ...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.
External linksProc Natl Acad Sci U S A / PubMed:37406093 / PubMed Central
MethodsEM (subtomogram averaging)
Resolution3.7 - 4.3 Å
Structure data

EMDB-15763: Untreatment WT HIV-1 immature gag
Method: EM (subtomogram averaging) / Resolution: 3.7 Å

EMDB-15764: PDDC treatment HIV immature Gag
Method: EM (subtomogram averaging) / Resolution: 4.3 Å

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