The Src kinase Lck facilitates assembly of HIV-1 at the plasma membrane.

The Src kinase Lck facilitates assembly of HIV-1 at the plasma membrane.
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SRC激酶LCK促进了质膜上HIV-1的组装。

DOI:
10.4049/jimmunol.181.5.3706
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发表时间:
2008-09-01
影响因子:
4.4
通讯作者:
Henderson, Andrew J.
Henderson, Andrew J.
中科院分区:
医学2区
文献类型:
--
作者:
Strasner, Amy B.;Natarajan, Malini;Doman, Tom;Key, Douglas;August, Avery;Henderson, Andrew J.

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HIV-1 assembly and egress are driven by the viral protein Gag and occur at the plasma membrane in T cells. Recent evidence indicates that secretory vesicles and machinery are essential components of virus packaging in both T cells and macrophages. However, the pathways and cellular mediators of Gag targeting to the plasma membrane are not well characterized. Lck, a lymphoid specific Src kinase critical for T cell activation, is found in the plasma membrane as well as various intracellular compartments and it has been suggested to influence HIV-1 replication. To investigate Lck as a potential regulator of Gag targeting, we assessed HIV-1 replication and Gag induced virus-like particle release in the presence and absence of Lck. Release of HIV-1 and virus like particles was reduced in the absence of Lck. This decrease in replication was not due to altered HIV-1 infection, transcription or protein translation. However, in T cells lacking Lck, HIV-1 accumulated intracellularly. In addition, expressing Lck in HeLa cells promoted HIV-1 Gag plasma membrane localization. Palmitoylation of the Lck unique domain, which is essential for directing Lck to the plasma membrane, was critical for its effect on HIV-1 replication. Furthermore, HIV-1 Gag directly interacted with the Lck unique domain in the context of infected cells. These results indicate that Lck plays a key role in targeting HIV-1 Gag to the plasma membrane in T cells.
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