Ströh Luisa J, Neu Ursula, Blaum Bärbel S, Buch Michael H C, Garcea Robert L, Stehle Thilo
Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.
Department of Molecular, Cellular and Developmental Biology and the BioFrontiers Institute, University of Colorado, Boulder, Colorado, USA.
J Virol. 2014 Sep;88(18):10831-9. doi: 10.1128/JVI.01084-14. Epub 2014 Jul 9.
Human polyomavirus 6 (HPyV6) and HPyV7 are commonly found on human skin. We have determined the X-ray structures of their major capsid protein, VP1, at resolutions of 1.8 and 1.7 Å, respectively. In polyomaviruses, VP1 commonly determines antigenicity as well as cell-surface receptor specificity, and the protein is therefore linked to attachment, tropism, and ultimately, viral pathogenicity. The structures of HPyV6 and HPyV7 VP1 reveal uniquely elongated loops that cover the bulk of the outer virion surfaces, obstructing a groove that binds sialylated glycan receptors in many other polyomaviruses. In support of this structural observation, interactions of VP1 with α2,3- and α2,6-linked sialic acids could not be detected in solution by nuclear magnetic resonance spectroscopy. Single-cell binding studies indicate that sialylated glycans are likely not required for initial attachment to cultured human cells. Our findings establish distinct antigenic properties of HPyV6 and HPyV7 capsids and indicate that these two viruses engage nonsialylated receptors.
Eleven new human polyomaviruses, including the skin viruses HPyV6 and HPyV7, have been identified during the last decade. In contrast to better-studied polyomaviruses, the routes of infection, cell tropism, and entry pathways of many of these new viruses remain largely mysterious. Our high-resolution X-ray structures of major capsid proteins VP1 from HPyV6 and from HPyV7 reveal critical differences in surface morphology from those of all other known polyomavirus structures. A groove that engages specific sialic acid-containing glycan receptors in related polyomaviruses is obstructed, and VP1 of HPyV6 and HPyV7 does not interact with sialylated compounds in solution or on cultured human cells. A comprehensive comparison with other structurally characterized polyomavirus VP1 proteins enhances our understanding of molecular determinants that underlie receptor specificity, antigenicity, and, ultimately, pathogenicity within the polyomavirus family and highlight the need for structure-based analysis to better define phylogenetic relationships within the growing polyomavirus family and perhaps also for other viruses.
人类多瘤病毒6（HPyV6）和HPyV7常见于人类皮肤。我们分别以1.8 Å和1.7 Å的分辨率测定了它们主要衣壳蛋白VP1的X射线结构。在多瘤病毒中，VP1通常决定抗原性以及细胞表面受体特异性，因此该蛋白与病毒的附着、嗜性以及最终的病毒致病性相关。HPyV6和HPyV7 VP1的结构显示出独特的细长环，这些环覆盖了病毒体大部分外部表面，阻塞了许多其他多瘤病毒中结合唾液酸化聚糖受体的凹槽。为支持这一结构观察结果，通过核磁共振光谱在溶液中未检测到VP1与α2,3 -和α2,6 -连接的唾液酸之间的相互作用。单细胞结合研究表明，唾液酸化聚糖可能不是病毒最初附着于培养的人类细胞所必需的。我们的研究结果确定了HPyV6和HPyV7衣壳独特的抗原特性，并表明这两种病毒利用非唾液酸化受体。
在过去十年中已鉴定出11种新的人类多瘤病毒，包括皮肤病毒HPyV6和HPyV7。与研究较为充分的多瘤病毒相比，许多这些新病毒的感染途径、细胞嗜性和进入途径在很大程度上仍然是个谜。我们对HPyV6和HPyV7主要衣壳蛋白VP1的高分辨率X射线结构揭示了其表面形态与所有其他已知多瘤病毒结构的关键差异。相关多瘤病毒中与特定含唾液酸聚糖受体结合的凹槽被阻塞，并且HPyV6和HPyV7的VP1在溶液中或培养的人类细胞上不与唾液酸化化合物相互作用。与其他具有结构特征的多瘤病毒VP1蛋白进行全面比较，增强了我们对多瘤病毒家族中受体特异性、抗原性以及最终致病性的分子决定因素的理解，并突出了基于结构的分析对于更好地定义不断增长的多瘤病毒家族内的系统发育关系以及可能对其他病毒的必要性。
