Institute for Virology and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
Department of Membrane Biochemistry, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.
Elife. 2019 May 20;8:e44345. doi: 10.7554/eLife.44345.
Oncogenic human papillomaviruses (HPV) are small DNA viruses that infect keratinocytes. After HPV binding to cell surface receptors, a cascade of molecular interactions mediates the infectious cellular internalization of virus particles. Aside from the virus itself, important molecular players involved in virus entry include the tetraspanin CD151 and the epidermal growth factor receptor (EGFR). To date, it is unknown how these components are coordinated in space and time. Here, we studied plasma membrane dynamics of CD151 and EGFR and the HPV16 capsid during the early phase of infection. We find that the proteinase ADAM17 activates the extracellular signal-regulated kinases (ERK1/2) pathway by the shedding of growth factors which triggers the formation of an endocytic entry platform. Infectious endocytic entry platforms carrying virus particles consist of two-fold larger CD151 domains containing the EGFR. Our finding clearly dissects initial virus binding from ADAM17-dependent assembly of a HPV/CD151/EGFR entry platform.
致癌型人类乳头瘤病毒（HPV）是一种感染角质细胞的小型 DNA 病毒。HPV 与细胞表面受体结合后，一连串的分子相互作用介导病毒颗粒的感染性细胞内化。除了病毒本身，病毒进入过程中涉及的重要分子参与者还包括四跨膜蛋白 CD151 和表皮生长因子受体（EGFR）。迄今为止，尚不清楚这些成分如何在空间和时间上协调。在这里，我们研究了 HPV16 衣壳在感染早期阶段时 CD151 和 EGFR 的质膜动力学。我们发现蛋白酶 ADAM17 通过生长因子的脱落激活细胞外信号调节激酶（ERK1/2）通路，从而触发内吞进入平台的形成。携带病毒颗粒的感染性内吞进入平台由包含 EGFR 的两倍大的 CD151 结构域组成。我们的发现清楚地区分了初始病毒结合与 ADAM17 依赖性 HPV/CD151/EGFR 进入平台的组装。
