Phosphoinositides direct equine infectious anemia virus gag trafficking and release.
Phosphoinositides direct equine infectious anemia virus gag trafficking and release.
复制标题
DOI：
10.1111/j.1600-0854.2010.01153.x
复制
发表时间：
2011-04
期刊：
影响因子：
--
通讯作者：
Carter CA
中科院分区：
文献类型：
--
作者：
Fernandes F;Chen K;Ehrlich LS;Jin J;Chen MH;Medina GN;Symons M;Montelaro R;Donaldson J;Tjandra N;Carter CA
Phosphatidylinositol 4,5-biphosphate (PI(4,5)P2), the predominant phosphoinositide on the plasma membrane, binds the matrix (MA) protein of Human Immunodeficiency Virus type 1 (HIV-1) and Equine Infectious Anemia Virus (EIAV) with similar affinities in vitro. Interaction with PI(4,5)P2 is critical for HIV-1 assembly on the plasma membrane. EIAV has been shown to localize in internal compartments hence the significance of its interaction with PI(4,5)P2 is unclear. We therefore investigated the binding in vitro of other phosphoinositides to EIAV MA and whether intracellular association with compartments bearing these phosphoinositides was important for assembly and release of virus-like particles (VLPs) formed by Gag. In vitro, EIAV MA bound PI(3)P with higher affinity than PI(4,5)P2 as revealed by NMR spectra upon lipid titration. Gag was detected on the plasma membrane and in compartments enriched in PI(3,5)P2. Treatment of cells with YM201636, a kinase inhibitor that blocks production of PI(3,5)P2 from PI(3)P, caused Gag to co-localize with aberrant compartments and inhibited VLP release. In contrast to HIV-1, release of EIAV VLPs was not significantly diminished by co-expression with 5-phosphatase IV, an enzyme that specifically depletes PI(4,5)P2 from the plasma membrane. However, co-expression with synaptojanin 2, a phosphatase with broader specificity, diminished VLP production. PI-binding pocket mutations caused striking budding defects, as revealed by electron microscopy. One of the mutations also modified Gag-Gag interaction, as suggested by altered bimolecular fluorescence complementation. We conclude that phosphoinositide-mediated targeting to peripheral and internal membranes is a critical factor in EIAV assembly and release.
登录
查看更多内容
影响因子：
1
作者：
Chen, Chaoping;Jin, Jing;Montelaro, Ronald C.
通讯作者：
Montelaro, Ronald C.
影响因子：
3.7
作者：
Kobayashi, T;Startchev, K;Gruenberg, J
通讯作者：
Gruenberg, J
影响因子：
4.8
作者：
Lawe, DC;Chawla, A;Corvera, S
通讯作者：
Corvera, S
影响因子：
4.8
作者：
Kisseleva, MV;Cao, L;Majerus, PW
通讯作者：
Majerus, PW
影响因子：
5.4
作者：
Ono, A;Freed, EO
通讯作者：
Freed, EO