Interactions of peptide triazole thiols with Env gp120 induce irreversible breakdown and inactivation of HIV-1 virions.
Interactions of peptide triazole thiols with Env gp120 induce irreversible breakdown and inactivation of HIV-1 virions.
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DOI：
10.1186/1742-4690-10-153
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发表时间：
2013-12-13
期刊：
影响因子：
3.3
通讯作者：
Chaiken I
中科院分区：
文献类型：
--
作者：
Bastian AR;Contarino M;Bailey LD;Aneja R;Moreira DR;Freedman K;McFadden K;Duffy C;Emileh A;Leslie G;Jacobson JM;Hoxie JA;Chaiken I
我们研究了肽三唑硫醇KR 13的潜在作用机制，KR 13先前已显示出特异性结合gp 120，阻断细胞受体位点相互作用并有效抑制HIV-1感染性。巯基封闭的KR 13 b及其亲本非巯基肽三唑HNG 156诱导gp 120脱落，但只有KR 13诱导p24衣壳蛋白释放。病毒裂解后得到的病毒体具有改变的形态，不含gp 120，但保留了与中和gp 41抗体结合的gp 41。值得注意的是，KR 13释放的HIV-1 p24被恩夫韦肽抑制，恩夫韦肽在膜融合过程中阻断gp 41 6-螺旋束的形成，而恩夫韦肽耐药病毒没有抑制p24的释放。因此，KR 13似乎诱导通常与膜融合和细胞进入相关的gp 41的结构变化。KR 13诱导的HIV-1 p24释放在HIV-1的几个进化枝以及完全感染性的HIV-1病毒体中观察到。KR 13的抗病毒活性及其在靶细胞接合之前消灭病毒体的能力表明肽三唑硫醇可以高度有效地抑制HIV穿过粘膜屏障的传播，并提供了一种新的探针来了解包膜内参与膜融合的生化信号。
We examined the underlying mechanism of action of the peptide triazole thiol, KR13 that has been shown previously to specifically bind gp120, block cell receptor site interactions and potently inhibit HIV-1 infectivity. KR13, the sulfhydryl blocked KR13b and its parent non-sulfhydryl peptide triazole, HNG156, induced gp120 shedding but only KR13 induced p24 capsid protein release. The resulting virion post virolysis had an altered morphology, contained no gp120, but retained gp41 that bound to neutralizing gp41 antibodies. Remarkably, HIV-1 p24 release by KR13 was inhibited by enfuvirtide, which blocks formation of the gp41 6-helix bundle during membrane fusion, while no inhibition of p24 release occurred for enfuvirtide-resistant virus. KR13 thus appears to induce structural changes in gp41 normally associated with membrane fusion and cell entry. The HIV-1 p24 release induced by KR13 was observed in several clades of HIV-1 as well as in fully infectious HIV-1 virions. The antiviral activity of KR13 and its ability to inactivate virions prior to target cell engagement suggest that peptide triazole thiols could be highly effective in inhibiting HIV transmission across mucosal barriers and provide a novel probe to understand biochemical signals within envelope that are involved in membrane fusion.
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影响因子：
3.4
作者：
Kamanna, Kantharaju;Aneja, Rachna;Duffy, Caitlin;Kubinski, Pamela;Moreira, Diogo Rodrigo;Bailey, Lauren D.;McFadden, Karyn;Schoen, Arne;Holmes, Andrew;Tuzer, Ferit;Contarino, Mark;Freire, Ernesto;Chaiken, Irwin M.
通讯作者：
Chaiken, Irwin M.
影响因子：
2.7
作者：
Gopi, Hosahudya;Cocklin, Simon;Pirrone, Vanessa;McFadden, Karyn;Tuzer, Ferit;Zentner, Isaac;Ajith, Sandya;Baxter, Sabine;Jawanda, Navneet;Krebs, Fred C.;Chaiken, Irwin M.
通讯作者：
Chaiken, Irwin M.
影响因子：
4.8
作者：
Champagne, Kelly;Shishido, Akira;Root, Michael J.
通讯作者：
Root, Michael J.
DOI：
10.1073/pnas.0801388105
发表时间：
2008-04-08
影响因子：
11.1
作者：
Bobardt, Michael D.;Cheng, Guofeng;Gallay, Philippe A.
通讯作者：
Gallay, Philippe A.
影响因子：
3.4
作者：
Gopi, Hosahudya N.;Tirupula, Kalyan C.;Chaiken, Irwin M.
通讯作者：
Chaiken, Irwin M.