Myricetin antagonizes semen-derived enhancer of viral infection (SEVI) formation and influences its infection-enhancing activity.
Myricetin antagonizes semen-derived enhancer of viral infection (SEVI) formation and influences its infection-enhancing activity.
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杨梅素拮抗精液源性病毒感染增强子 (SEVI) 的形成并影响其感染增强活性
DOI：
10.1186/s12977-018-0432-3
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发表时间：
2018-07-16
期刊：
影响因子：
3.3
通讯作者：
Li L
中科院分区：
文献类型：
--
作者：
Ren R;Yin S;Lai B;Ma L;Wen J;Zhang X;Lai F;Liu S;Li L
精液是人类免疫缺陷病毒（HIV）性传播的重要载体，含有可显著增强HIV感染的精液淀粉样纤维。精液源性病毒感染增强子（SEVI）是精液淀粉样纤维的最佳特征之一。由于它们的高度阳离子性质，SEVI原纤维可以捕获HIV病毒体，增加病毒对靶细胞的附着，并增强病毒融合。一些研究报道，杨梅素拮抗淀粉样β蛋白（Aβ）的形成;杨梅素在体外也显示出很强的抗HIV活性。在这里，我们报告说，杨梅素抑制SEVI原纤维的形成，通过结合到淀粉样蛋白的区域的SEVI前体肽（PAP 248 -286）和破坏PAP 248 -286寡聚化。此外，发现杨梅素重塑预先形成的SEVI纤维，并影响SEVI促进HIV-1感染的活性。此外，在精液中，杨梅素与其他抗逆转录病毒药物联合对HIV-1感染显示出协同作用。将杨梅素掺入具有抗SEVI和抗HIV活性的双功能杀微生物剂组合中是预防HIV性传播的非常有希望的方法。本文的在线版本（10.1186/s12977-018-0432-3）包含补充材料，可供授权用户使用。
Semen is a critical vector for human immunodeficiency virus (HIV) sexual transmission and harbors seminal amyloid fibrils that can markedly enhance HIV infection. Semen-derived enhancer of viral infection (SEVI) is one of the best-characterized seminal amyloid fibrils. Due to their highly cationic properties, SEVI fibrils can capture HIV virions, increase viral attachment to target cells, and augment viral fusion. Some studies have reported that myricetin antagonizes amyloid β-protein (Aβ) formation; myricetin also displays strong anti-HIV activity in vitro. Here, we report that myricetin inhibits the formation of SEVI fibrils by binding to the amyloidogenic region of the SEVI precursor peptide (PAP248–286) and disrupting PAP248–286 oligomerization. In addition, myricetin was found to remodel preformed SEVI fibrils and to influence the activity of SEVI in promoting HIV-1 infection. Moreover, myricetin showed synergistic effects against HIV-1 infection in combination with other antiretroviral drugs in semen. Incorporation of myricetin into a combination bifunctional microbicide with both anti-SEVI and anti-HIV activities is a highly promising approach to preventing sexual transmission of HIV. The online version of this article (10.1186/s12977-018-0432-3) contains supplementary material, which is available to authorized users.
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影响因子：
15
作者：
Nanga, Ravi P. R.;Brender, Jeffrey R.;Vivekanandan, Subramanian;Popovych, Nataliya;Ramamoorthy, Ayyalusamy
通讯作者：
Ramamoorthy, Ayyalusamy
影响因子：
3.3
作者：
Kim KA;Yolamanova M;Zirafi O;Roan NR;Staendker L;Forssmann WG;Burgener A;Dejucq-Rainsford N;Hahn BH;Shaw GM;Greene WC;Kirchhoff F;Münch J
通讯作者：
Münch J
影响因子：
4.2
作者：
Castellano LM;Shorter J
通讯作者：
Shorter J
影响因子：
6.1
作者：
Li, Richan;Liu, Teng;Yang, Jie
通讯作者：
Yang, Jie
影响因子：
4.8
作者：
LoRicco, Josephine G.;Xu, Changmingzi Sherry;Makhatadze, George I.
通讯作者：
Makhatadze, George I.