Secretory leukocyte protease inhibitor binds to annexin II, a cofactor for macrophage HIV-1 infection.

Secretory leukocyte protease inhibitor binds to annexin II, a cofactor for macrophage HIV-1 infection.
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分泌的白细胞蛋白酶抑制剂与膜联蛋白II(一种用于巨噬细胞HIV-1感染的辅助因子)结合。

DOI:
10.1084/jem.20041115
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发表时间:
2004-11-15
影响因子:
15.3
通讯作者:
Wahl, SM
Wahl, SM
中科院分区:
医学1区
文献类型:
--
作者:
Ma, G;Greenwell-Wild, T;Lei, KJ;Jin, WW;Swisher, J;Hardegen, N;Wild, CT;Wahl, SM

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分泌性白细胞蛋白酶抑制剂(SLPI)在入口处的分布表明其参与保护宿主免受病原体的侵害,这与SLPI通过未知机制抑制人类免疫缺陷病毒(HIV)-1感染的能力一致。我们现在证明SLPI通过磷脂结合蛋白膜联蛋白II与人巨噬细胞膜结合。基于最近鉴定的人类细胞膜磷脂酰丝氨酸(PS)在HIV-1的外套,我们定义了一个新的作用膜联蛋白II,PS结合部分,作为支持巨噬细胞HIV-1感染的细胞辅因子。此外,这种HIV-1 PS与膜联蛋白II的相互作用可以被SLPI或其他膜联蛋白II特异性抑制剂破坏。PS-膜联蛋白II连接可能代表预防HIV-1感染的新靶点。
The distribution of secretory leukocyte protease inhibitor (SLPI) at entry portals indicates its involvement in defending the host from pathogens, consistent with the ability of SLPI to inhibit human immunodeficiency virus (HIV)-1 infection by an unknown mechanism. We now demonstrate that SLPI binds to the membrane of human macrophages through the phospholipid-binding protein, annexin II. Based on the recent identification of human cell membrane phosphatidylserine (PS) in the outer coat of HIV-1, we define a novel role for annexin II, a PS-binding moiety, as a cellular cofactor supporting macrophage HIV-1 infection. Moreover, this HIV-1 PS interaction with annexin II can be disrupted by SLPI or other annexin II–specific inhibitors. The PS–annexin II connection may represent a new target to prevent HIV-1 infection.
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