Zhou Run-Hong, Guo Le, Liu Jin-Biao, Liu Hang, Hou Wei, Ma Tong-Cui, Wang Xu, Wu Jian-Guo, Ye Li, Ho Wen-Zhe, Li Jie-Liang
*School of Basic Medical Sciences/State Key Laboratory of Virology, Wuhan University, Wuhan, China; †Department of Pathology and Laboratory Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, PA; and ‡School of Public Health, Guangxi Medical University, Nanning, China.
J Acquir Immune Defic Syndr. 2017 Jun 1;75(2):232-240. doi: 10.1097/QAI.0000000000001361.
Human semen contains a factor that can enhance HIV infection up to 10-fold in cultures. This factor is termed semen-derived enhancer of virus infection (SEVI) and is composed of proteolytic fragments (PAP248-286) from prostatic acid phosphatase in semen. In this study, 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 epigallocatechin gallate (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 EGCG. The mixture was added to cultures of TZM-bl cells or macaque PBMCs. The effect of EGCG on macaque SEVI was measured by Congo-red staining assay and thioflavin T (ThT) fluorescence assay and was 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 PBMCs. 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.
人类精液中含有一种因子，在培养物中可使HIV感染增强达10倍。这种因子被称为精液衍生病毒感染增强剂（SEVI），由精液中前列腺酸性磷酸酶的蛋白水解片段（PAP248 - 286）组成。在本研究中，我们检测了猕猴SEVI是否能促进猴免疫缺陷病毒（SIV）或嵌合猴/人免疫缺陷病毒（SHIV）感染。我们还研究了表没食子儿茶素没食子酸酯（EGCG）对猕猴SEVI介导的SIV或SHIV增强作用的影响。
在有或没有EGCG存在的情况下，将SIV或SHIV与不同浓度的猕猴SEVI混合。将混合物加入TZM - bl细胞或猕猴外周血单个核细胞（PBMCs）培养物中。通过刚果红染色试验和硫黄素T（ThT）荧光试验测定EGCG对猕猴SEVI的影响，并通过透射电子显微镜观察。
我们发现人类PAP248 - 286与猕猴PAP248 - 286在277位点存在一个氨基酸差异。猕猴SEVI显著增强了TZM - bl细胞和猕猴PBMCs对SIV或SHIV的感染。EGCG可阻断猕猴SEVI介导的SIV或SHIV感染增强作用。从机制上讲，EGCG可降解促进HIV附着于靶细胞的猕猴SEVI淀粉样纤维的形成。
猕猴SEVI可增强SIV或SHIV感染这一发现表明在猕猴模型的体内研究中使用猕猴SEVI的可能性。此外，未来有必要研究EGCG是否可作为预防SIV或SHIV黏膜传播的有效杀菌剂。
