Neutral sphingomyelinase 2 is required for HIV-1 maturation

被引：8
作者：
Waheed, Abdul A. [1 ]
Zhu, Yanan [2 ]
Agostino, Eva [1 ]
Naing, Lwar [1 ]
Hikichi, Yuta [1 ]
Soheilian, Ferri [3 ]
Yoo, Seung- Wan [4 ]
Song, Yun [5 ]
Zhang, Peijun [2 ,5 ,6 ]
Slusher, Barbara S. [4 ,7 ,8 ]
Haughey, Norman J. [4 ,8 ]
Freed, Eric O. [1 ]
机构：
[1] NCI, Virus Cell Interact Sect, HIV Dynam & Replicat Program, Ctr Canc Res, Frederick, MD 21702 USA
[2] Univ Oxford, Wellcome Trust Ctr Human Genet, Div Struct Biol, Oxford OX3 7BN, England
[3] Frederick Natl Lab Canc Res, Canc Res Technol Program, Electron Microscopy Lab, Frederick, MD 21702 USA
[4] Johns Hopkins Univ, Dept Neurol, Sch Med, Baltimore, MD 21287 USA
[5] Diamond Light Source, Electron Bioimaging Ctr, Harwell Sci & Innovat Campus, Didcot OX11 0DE, England
[6] Univ Oxford, Chinese Acad Med Sci, Oxford Inst, Oxford OX3 7BN, England
[7] Johns Hopkins Univ, Johns Hopkins Drug Discovery, Sch Med, Baltimore, MD 21287 USA
[8] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Sch Med, Baltimore, MD 21287 USA
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2023年 / 120卷 / 28期
基金：
英国生物技术与生命科学研究理事会;
关键词：
HIV-1; nSMase2; Gag processing; maturation; infectivity; HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; VIRION-ASSOCIATED CHOLESTEROL; INFECTIOUS-ANEMIA VIRUS; B METHYL-ESTER; PLASMA-MEMBRANE; TYPE-1; GAG; LIPID RAFTS; PARTICLE-PRODUCTION; PROTEINASE DIMER;
D O I：
10.1073/pnas.2219475120
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
HIV -1 assembly occurs at the inner leaflet of the plasma membrane (PM) in highly ordered membrane microdomains. The size and stability of membrane microdo-mains is regulated by activity of the sphingomyelin hydrolase neutral sphingomyeli-nase 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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页数：12
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