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.

引用

页数：12

共 101 条

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