Secreted phospholipases A2, a new class of HIV inhibitors that block virus entry into host cells
Secreted phospholipases A2, a new class of HIV inhibitors that block virus entry into host cells
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DOI：
10.1172/jci6915
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发表时间：
1999-09-01
影响因子：
15.9
通讯作者：
Doglio, A
中科院分区：
文献类型：
--
作者：
Fenard, D;Lambeau, G;Doglio, A
哺乳动物和毒液分泌的磷脂酶A（2）（sPLA（2）s）具有多种生物学效应。在这里，我们表明，几个sPLA（2）的保护人类初级血液白细胞从各种巨噬细胞的复制和。嗜T细胞HIV-1毒株。sPLA（2）s的抑制作用既不是由于杀病毒作用，也不是由于对宿主细胞的细胞毒性作用，而是涉及一种更特异的机制。sPLA（2）s对病毒与细胞的结合和合胞体的形成没有影响，但它们阻止了病毒衣壳蛋白在细胞内的释放，这表明sPLA（2）s在病毒粒子脱壳之前阻断了病毒进入细胞，并且与辅助受体的使用无关。sPLA（2）s的各种抑制剂和催化产物对HIV-1感染没有影响，表明sPLA（2）的催化活性不参与抗病毒作用。相反，抗病毒活性似乎涉及sPLA（2）与宿主细胞的特异性相互作用。事实上，在11种来自毒液和哺乳动物组织的sPLA（2）中，发现4种毒液sPLA（2）是非常有效的HIV-1抑制剂（ID 50 < 1 nM），并且还以高亲和力（K-0.5 < 1 nM）特异性结合宿主细胞。尽管哺乳动物胰腺IB组和炎症型IIA组sPLA（2）对HIV-1复制无活性，但我们的结果可能具有生理学意义，因为新型sPLA（2）正在人类中进行表征。
Mammalian and venom secreted phospholipases A(2) (sPLA(2)s) have been associated with a variety of biological effects. Here we show that several sPLA(2)s protect human primary blood leukocytes from the replication of various macrophage and. T cell-tropic HIV-1 strains. Inhibition by sPLA(2)s results neither from a virucidal effect nor from a cytotoxic effect on host cells, but it involves a more specific mechanism. sPLA(2)s have no effect on virus binding to cells nor on syncytia formation, but they prevent the intracellular release of the viral capsid protein, suggesting that sPLA(2)s block viral entry into cells before virion uncoating and independently of the coreceptor usage. Various inhibitors and catalytic products of sPLA(2)s have no effect on HIV-1 infection, suggesting that sPLA(2) catalytic activity is not involved in the antiviral effect. Instead, the antiviral activity appears to involve a specific interaction of sPLA(2)s to host cells. Indeed, of 11 sPLA(2)s from venom and mammalian tissues assayed, 4 venom sPLA(2)s were found to be very potent HIV-1 inhibitors (ID50 < 1 nM) and also to bind specifically to host cells with high affinities (K-0.5 < 1 nM). Although mammalian pancreatic group IB and inflammatory-type group IIA sPLA(2)s were inactive against HIV-1 replication, our results could be of physiological interest, as novel sPLA(2)s are being characterized in humans.