Elias Abigail K, Scanlon Denis, Musgrave Ian F, Carver John A
School of Chemistry and Physics, The University of Adelaide, South Australia 5005, Australia.
Discipline of Pharmacology, School of Medical Sciences, The University of Adelaide, South Australia 5005, Australia.
Biochim Biophys Acta. 2014 Sep;1844(9):1591-8. doi: 10.1016/j.bbapap.2014.06.006. Epub 2014 Jun 17.
Semen-derived enhancer of viral infection (SEVI) is the term given to the amyloid fibrils formed by a 39-amino acid fragment (PAP248-286) of prostatic acidic phosphatase (PAP) found in human semen. SEVI enhances human immunodeficiency virus (HIV) infectivity by four to five orders of magnitude (Münch et al., 2007). Here, we show by various biophysical techniques including Thioflavin T fluorescence, circular dichroism spectroscopy and transmission electron microscopy that fragments encompassing the central region of SEVI, i.e. PAP248-271 and PAP257-267, form fibrils of similar morphology to SEVI. Our results show that the central region, residues PAP267-271, is crucially important in promoting SEVI fibril formation. Furthermore, SEVI and fibrillar forms of these peptide fragments are toxic to neuronal pheochromocytoma 12 cells but not to epithelial colon carcinoma cells. These findings imply that although SEVI assists in the attachment of HIV-1 to immune cells, it may not facilitate HIV entry by damaging the epithelial cell layer that presents a barrier to the HIV.
精液衍生病毒感染增强因子（SEVI）是指在人类精液中发现的由前列腺酸性磷酸酶（PAP）的一个39个氨基酸片段（PAP248 - 286）形成的淀粉样原纤维。SEVI可将人类免疫缺陷病毒（HIV）的感染性提高4至5个数量级（Münch等人，2007年）。在此，我们通过多种生物物理技术，包括硫黄素T荧光、圆二色光谱和透射电子显微镜，表明包含SEVI中心区域的片段，即PAP248 - 271和PAP257 - 267，形成了与SEVI形态相似的原纤维。我们的结果表明，中心区域，即PAP267 - 271残基，在促进SEVI原纤维形成中至关重要。此外，SEVI和这些肽片段的纤维状形式对神经母细胞瘤12细胞有毒性，但对上皮结肠癌细胞无毒。这些发现意味着，尽管SEVI有助于HIV - 1附着于免疫细胞，但它可能不会通过破坏对HIV构成屏障的上皮细胞层来促进HIV进入。
