Department of Dermatology, McGovern Medical School at Houston, Houston, TX, USA.
Baylor College of Medicine, Houston, TX, USA.
J Eur Acad Dermatol Venereol. 2017 Aug;31(8):1338-1341. doi: 10.1111/jdv.14326. Epub 2017 Jun 6.
Trichodysplasia spinulosa (TS) is a disfiguring folliculocentric cutaneous disease caused by infection with the trichodysplasia spinulosa polyomavirus (TSPyV). The TSPyV genome contains splice variants encoding the middle tumour (mT) antigen, although the potential role for TSPyV mT antigen in disease development remains unknown.
The current study was designed to investigate the mechanistic properties of TSPyV mT antigen, which may further our understanding of TS pathogenesis and provide insight into potential therapies.
A lentiviral packaging system was used to create an inducible cell line expressing TSPyV mT antigen. Proteins were extracted, separated by SDS-PAGE and subjected to Western blot analysis. Co-immunoprecipitation experiments and mutational analyses were also performed to evaluate protein-protein interactions of mT antigen.
We describe a novel mechanism of action for mT antigen that involves hyperactivation of MEK, ERK and MNK1. Our findings suggest that dysregulation of these key signalling molecules depends upon TSPyV mT antigen interaction with protein phosphatase 2A (PP2A) via intact Zn binding motifs.
Given that PP2A interaction and MEK/ERK/MNK1 phosphorylation are associated with high levels of cell proliferation and inflammation, our findings provide new evidence that TSPyV mT antigen may contribute to the pro-proliferative conditions that lead to TS development.
毛发疏松症（TS）是一种由毛发疏松多瘤病毒（TSPyV）感染引起的以毛囊为中心的毁容性皮肤疾病。TSPyV 基因组包含编码中间肿瘤（mT）抗原的剪接变体，尽管 TSPyV mT 抗原在疾病发展中的潜在作用尚不清楚。
本研究旨在研究 TSPyV mT 抗原的机制特性，这可能进一步加深我们对 TS 发病机制的理解，并为潜在的治疗方法提供思路。
使用慢病毒包装系统构建了表达 TSPyV mT 抗原的诱导细胞系。提取蛋白，通过 SDS-PAGE 分离，然后进行 Western blot 分析。还进行了共免疫沉淀实验和突变分析，以评估 mT 抗原的蛋白-蛋白相互作用。
我们描述了 mT 抗原的一种新的作用机制，涉及 MEK、ERK 和 MNK1 的过度激活。我们的研究结果表明，这些关键信号分子的失调依赖于 TSPyV mT 抗原与蛋白磷酸酶 2A（PP2A）通过完整的 Zn 结合基序相互作用。
鉴于 PP2A 相互作用和 MEK/ERK/MNK1 磷酸化与高水平的细胞增殖和炎症有关，我们的研究结果提供了新的证据，表明 TSPyV mT 抗原可能有助于导致 TS 发展的促增殖条件。
