Van Doorslaer Koenraad, Sidi Abdellahi Ould M'hamed Ould, Zanier Katia, Rybin Vladimir, Deryckère François, Rector Annabel, Burk Robert D, Lienau E Kurt, van Ranst Marc, Travé Gilles
Laboratory of Clinical Virology, Rega Institute for Medical Research, University of Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium.
J Virol. 2009 Sep;83(17):8759-70. doi: 10.1128/JVI.01777-08. Epub 2009 Jun 24.
Papillomaviruses (PVs) are a large family of small DNA viruses infecting mammals, reptiles, and birds. PV infection induces cell proliferation that may lead to the formation of orogenital or skin tumors. PV-induced cell proliferation has been related mainly to the expression of two small oncoproteins, E6 and E7. In mammalian PVs, E6 contains two 70-residue zinc-binding repeats, whereas E7 consists of a natively unfolded N-terminal region followed by a zinc-binding domain which folds as an obligate homodimer. Here, we show that both the novel francolin bird PV Francolinus leucoscepus PV type 1 (FlPV-1) and the chaffinch bird PV Fringilla coelebs PV contain unusual E6 and E7 proteins. The avian E7 proteins contain an extended unfolded N terminus and a zinc-binding domain of reduced size, whereas the avian E6 proteins consist of a single zinc-binding domain. A comparable single-domain E6 protein may have existed in a common ancestor of mammalian and avian PVs. Mammalian E6 C-terminal domains are phylogenetically related to those of single-domain avian E6, whereas mammalian E6 N-terminal domains seem to have emerged by duplication and subsequently diverged from the original ancestral domain. In avian and mammalian cells, both FlPV-1 E6 and FlPV-1 E7 were evenly expressed in the cytoplasm and the nucleus. Finally, samples of full-length FlPV-1 E6 and the FlPV-1 E7 C-terminal zinc-binding domain were prepared for biophysical analysis. Both constructs were highly soluble and well folded, according to nuclear magnetic resonance spectroscopy measurements.
乳头瘤病毒（PVs）是一大类感染哺乳动物、爬行动物和鸟类的小型DNA病毒。PV感染会诱导细胞增殖，这可能导致口生殖器或皮肤肿瘤的形成。PV诱导的细胞增殖主要与两种小的癌蛋白E6和E7的表达有关。在哺乳动物PV中，E6包含两个70个残基的锌结合重复序列，而E7由一个天然未折叠的N端区域和一个折叠为专一性同二聚体的锌结合结构域组成。在这里，我们表明新型鹧鸪鸟PV白喉鹧鸪PV 1型（FlPV-1）和苍头燕雀鸟PV苍头燕雀PV都含有不寻常的E6和E7蛋白。禽类E7蛋白包含一个延长的未折叠N端和一个尺寸减小的锌结合结构域，而禽类E6蛋白由单个锌结合结构域组成。一种类似的单结构域E6蛋白可能存在于哺乳动物和禽类PV的共同祖先中。哺乳动物E6的C端结构域在系统发育上与单结构域禽类E6的相关，而哺乳动物E6的N端结构域似乎是通过复制出现的，随后从原始祖先结构域分化而来。在禽类和哺乳动物细胞中，FlPV-1 E6和FlPV-1 E7均在细胞质和细胞核中均匀表达。最后，制备了全长FlPV-1 E6和FlPV-1 E7 C端锌结合结构域的样品用于生物物理分析。根据核磁共振光谱测量，这两种构建体都高度可溶且折叠良好。
