Epigallocatechin Gallate Inhibits Macaque SEVI-Mediated Enhancement of SIV or SHIV Infection.
Epigallocatechin Gallate Inhibits Macaque SEVI-Mediated Enhancement of SIV or SHIV Infection.
复制标题
DOI：
10.1097/qai.0000000000001361
复制
发表时间：
2017-06-01
期刊：
影响因子：
--
通讯作者：
Li JL
中科院分区：
文献类型：
--
作者：
Zhou RH;Guo L;Liu JB;Liu H;Hou W;Ma TC;Wang X;Wu JG;Ye L;Ho WZ;Li JL
人类精液中含有一种因子，在培养中可使HIV感染增加高达105倍。该因子被称为SEVI(精液来源的病毒感染增强因子)，由精液中前列腺酸性磷酸酶(PAP)的蛋白分解片段(PAP248-286)组成。在这里，我们研究了猕猴SEVI是否可以促进猴免疫缺陷病毒(SIV)或嵌合的猴/人类免疫缺陷病毒(SHIV)的感染。我们还研究了EGCG对猕猴SEVI介导的SIV或SIV增强的影响。SIV或SIV与不同浓度的猕猴SEVI在有或没有表没食子儿茶素没食子酸酯(EGCG)的情况下混合。将该混合物加入TZM-bl细胞或猕猴PBMC的培养中。采用刚果红染色法、硫代黄素T(THT)荧光法和透射电子显微镜观察EGCG对猕猴SEVI的影响。我们发现人的PAP248-286与猕猴的PAP248-286在277位有一个氨基酸差异。猕猴SEVI可显著增强SIV或SIV对TZM-bl细胞和猕猴PBMC的感染。EGCG可阻断恒河猴SEVI介导的SIV或SIV感染增强。从机制上讲，EGCG可以减少猕猴SEVI淀粉样纤维的形成，这种纤维有助于HIV附着到靶细胞上。猕猴SEVI可以增加SIV或SIV的感染，这一发现表明了将猕猴SEVI用于猕猴模型体内研究的可能性。此外，有必要进一步研究EGCG是否可以作为一种有效的杀菌剂来预防SIV或SIV粘膜传播。
Human semen contains a factor that can enhance HIV infection up to 10^5-fold in cultures. This factor is termed SEVI (Semen-derived Enhancer of Virus Infection), which is composed of proteolytic fragments (PAP248-286) from prostatic acid phosphatase (PAP) in semen. Here, we examined whether macaque SEVI can facilitate simian immunodeficiency virus (SIV) or chimeric simian/human immunodeficiency virus (SHIV) infection. We also studied the effect of EGCG on macaque SEVI-mediated SIV or SHIV enhancement. SIV or SHIV was mixed with different concentrations of macaque SEVI in the presence or absence of epigallocatechin gallate (EGCG). The mixture was added to cultures of TZM-bl cells or macaque PBMC. The effect of EGCG on macaque SEVI was measured by Congo-red staining assay, thioflavin T (ThT) fluorescence assay and visualized by a transmission electron microscope. We identified that there is one amino acid difference at the site of 277 between human PAP248-286 and macaque PAP248-286. Macaque SEVI significantly enhanced SIV or SHIV infection of TZM-bl cells and macaque PBMC. EGCG could block macaque SEVI-mediated enhancement of SIV or SHIV infection. Mechanistically, EGCG could degrade the formation of macaque SEVI amyloid fibrils that facilitates HIV attachment to the target cells. The finding that macaque SEVI could enhance SIV or SHIV infection indicates the possibility to use the macaque SEVI in vivo studies with the macaque models. In addition, future studies are necessary to examine whether EGCG can be used as an effective microbicide for preventing SIV or SHIV mucosal transmission.