Chen Jinquan, Ren Ruxia, Tan Suiyi, Zhang Wanyue, Zhang Xuanxuan, Yu Fei, Xun Tianrong, Jiang Shibo, Liu Shuwen, Li Lin
School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
Key Laboratory of Medical Molecular Virology of MOE/MOH, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai, China.
PLoS One. 2015 Dec 14;10(12):e0144522. doi: 10.1371/journal.pone.0144522. eCollection 2015.
Semen is a major vehicle for HIV transmission. Prostatic acid phosphatase (PAP) fragments, such as PAP248-286, in human semen can form amyloid fibrils to enhance HIV infection. Other endogenous or exogenous factors present during sexual intercourse have also been reported to promote the formation of seminal amyloid fibrils.
Here, we demonstrated that a synthetic 15-residue peptide derived from the HIV-1 gp120 coreceptor-binding region, designated enhancing peptide 2 (EP2), can rapidly self-assemble into nanofibers. These EP2-derivated nanofibers promptly accelerated the formation of semen amyloid fibrils by PAP248-286, as shown by Thioflavin T (ThT) and Congo red assays. The amyloid fibrils presented similar morphology, assessed via transmission electron microscopy (TEM), in the presence or absence of EP2. Circular dichroism (CD) spectroscopy revealed that EP2 accelerates PAP248-286 amyloid fibril formation by promoting the structural transition of PAP248-286 from a random coil into a cross-β-sheet. Newly formed semen amyloid fibrils effectively enhanced HIV-1 infection in TZM-bl cells and U87 cells by promoting the binding of HIV-1 virions to target cells.
Nanofibers composed of EP2 promote the formation of PAP248-286 amyloid fibrils and enhance HIV-1 infection.
精液是艾滋病毒传播的主要载体。人类精液中的前列腺酸性磷酸酶（PAP）片段，如PAP248 - 286，可形成淀粉样原纤维以增强艾滋病毒感染。据报道，性交过程中存在的其他内源性或外源性因素也会促进精液淀粉样原纤维的形成。
在此，我们证明了一种源自HIV - 1 gp120共受体结合区域的合成15肽，命名为增强肽2（EP2），能够迅速自组装成纳米纤维。硫黄素T（ThT）和刚果红检测显示，这些源自EP2的纳米纤维迅速加速了PAP248 - 286诱导的精液淀粉样原纤维的形成。通过透射电子显微镜（TEM）评估，无论有无EP2，淀粉样原纤维呈现出相似的形态。圆二色性（CD）光谱表明，EP2通过促进PAP248 - 286从无规卷曲结构转变为交叉β-折叠结构来加速其淀粉样原纤维的形成。新形成的精液淀粉样原纤维通过促进HIV - 1病毒粒子与靶细胞的结合，有效增强了TZM - bl细胞和U87细胞中的HIV - 1感染。
由EP2组成的纳米纤维促进PAP248 - 286淀粉样原纤维的形成并增强HIV - 1感染。
