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晶状体上皮源性生长因子(lens epithelium-derived growth factor,LEDGF)又名p75蛋白是人类免疫缺陷病毒1型(human immunodeficiency virus type 1,HIV-1)整合过程中不可缺少的细胞辅助因子。LEDGF/p75将整合酶链合到特定的DNA序列上,促进链转移反应和整合的完成。LEDGF/p75对整合酶具有稳定作用,在LEDGF/p75缺陷的感染细胞中,整合酶很快被降解,HIV-1的复制和感染被阻断,大量研究证明干扰LEDGF/p75的作用是抑制HIV复制感染的有效途径。而LEDGF/p75与整合酶结合的三维晶体结构已被解析,并通过高通量筛选获得了该细胞辅助因子的抑制剂。本文综述了LEDGF/p75的结构功能、与整合酶作用的机制以及基于该细胞辅助因子的抑制剂研究。
The lens epithelium-derived growth factor (LEDGF), also called p75 protein, is an indispensable cofactor for the integration of human immunodeficiency virus type 1 (HIV-1). LEDGF / p75 integrates integrase into specific DNA sequences, facilitating chain transfer reactions and integration. LEDGF / p75 has a stabilizing effect on integrase. Integrase degraded rapidly in LEDGF / p75-deficient infected cells and the replication and infection of HIV-1 is blocked. Numerous studies have shown that interference with LEDGF / p75 inhibits HIV An effective way to replicate infection. The three-dimensional crystal structure of LEDGF / p75 binding to integrase has been resolved and inhibitors of this cofactor have been obtained by high-throughput screening. This review summarizes the structural function of LEDGF / p75, its mechanism of action as an integrase, and the study of inhibitors based on this cofactor.