Baker Institute for Animal Health, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Department of Medicine, Penn State University College of Medicine, Hershey, Pennsylvania, USA.
J Virol. 2019 Mar 5;93(6). doi: 10.1128/JVI.01542-18. Print 2019 Mar 15.
Parvovirus-derived endogenous viral elements (EVEs) have been found in the genomes of many different animal species, resulting from integration events that may have occurred from more than 50 million years ago to much more recently. Here, we further investigate the properties of autonomous parvovirus EVEs and describe their relationships to contemporary viruses. While we did not find any intact capsid protein open reading frames in the integrated viral sequences, we examined three EVEs that were repaired to form full-length sequences with relatively few changes. These sequences were found in the genomes of (brown rat), (Algerian mouse), and (wood mouse). The sequence was not present in the genomes of the closely related species , , , and , indicating that it was less than 2 million years old, and the and sequences were not found in the published genomes of other mouse species, also indicating relatively recent insertions. The VP2 sequence assembled into capsids, which had high thermal stability, bound the sialic acid -acetylneuraminic acid, and entered murine L cells. The 3.89-Å structure of the virus-like particles (VLPs), determined using cryo-electron microscopy, showed similarities to rodent and porcine parvovirus capsids. The repaired VP2 sequences from and did not assemble as first prepared, but chimeras combining capsid surface loops from with canine parvovirus assembled, allowing some of that capsid's structures and functions to be examined. Parvovirus endogenous viral elements (EVEs) that have been incorporated into the genomes of different animals represent remnants of the DNA sequences of ancient viruses that infected the ancestors of those animals millions of years ago, but we know little about their properties or how they differ from currently circulating parvoviruses. By expressing the capsid proteins of different parvovirus EVEs that were found integrated into the genomes of three different rodents, we can examine their structures and functions. A VP2 (major capsid protein) EVE sequence from a mouse genome assembled into capsids that had a similar structure and biophysical properties to extant parvoviruses and also bound sialic acids and entered rodent cells. Chimeras formed from combinations of canine parvovirus and portions of the parvovirus sequences from the brown rat genome allowed us to examine the structures and functions of the surface loops of that EVE capsid.
parvovirus 衍生的内源性病毒元件 (EVEs) 已在许多不同动物物种的基因组中发现，这是由于整合事件导致的，这些整合事件可能发生在 5000 多万年前甚至更近。在这里，我们进一步研究了自主 parvovirus EVEs 的特性，并描述了它们与当代病毒的关系。虽然我们在整合的病毒序列中没有发现任何完整的衣壳蛋白开放阅读框，但我们检查了三个 EVEs，它们通过修复形成了具有相对较少变化的全长序列。这些序列存在于 （褐家鼠）、 （阿尔及利亚鼠）和 （林姬鼠）的基因组中。 序列不存在于密切相关的物种 、 、 、 基因组中，表明它的年龄不到 200 万年，而 序列和 序列也不存在于其他已发表的鼠种基因组中，这也表明它们是最近插入的。组装成衣壳的 VP2 序列具有高热稳定性，结合了唾液酸 -乙酰神经氨酸，并进入了小鼠 L 细胞。使用冷冻电子显微镜确定的 3.89-Å 病毒样颗粒 (VLPs) 结构显示与啮齿动物和猪细小病毒衣壳相似。来自 和 的修复 VP2 序列最初没有组装，但将 衣壳表面环的嵌合体与犬细小病毒组装在一起，允许检查该衣壳的一些结构和功能。已整合到不同动物基因组中的 parvovirus 内源性病毒元件 (EVEs) 代表了感染这些动物祖先的古代病毒的 DNA 序列的残余物，但我们对它们的特性或它们与当前循环的 parvoviruses 有何不同知之甚少。通过表达在三种不同啮齿动物基因组中发现的不同 parvovirus EVEs 的衣壳蛋白，我们可以检查它们的结构和功能。来自鼠基因组的 VP2（主要衣壳蛋白）EVE 序列组装成的衣壳具有与现存 parvoviruses 相似的结构和生物物理特性，并且还结合了唾液酸并进入了啮齿动物细胞。由犬细小病毒和来自褐家鼠基因组的 parvovirus 序列部分形成的嵌合体使我们能够检查该 EVE 衣壳表面环的结构和功能。
