Evolutionary reconstructions of the transferrin receptor of Caniforms supports canine parvovirus being a re-emerged and not a novel pathogen in dogs.
Evolutionary reconstructions of the transferrin receptor of Caniforms supports canine parvovirus being a re-emerged and not a novel pathogen in dogs.
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DOI：
10.1371/journal.ppat.1002666
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发表时间：
2012
期刊：
影响因子：
6.7
通讯作者：
Parrish CR
中科院分区：
文献类型：
--
作者：
Kaelber JT;Demogines A;Harbison CE;Allison AB;Goodman LB;Ortega AN;Sawyer SL;Parrish CR
细小病毒利用转铁蛋白受体1型（TfR）进入食肉动物细胞，特异性相互作用是控制宿主范围的关键。我们发现，在犬（狗和相关物种）的进化过程中获得的TfR的几个关键突变修改了与细小病毒衣壳的相互作用，通过降低结合水平。这些数据，沿着TFRC基因中正选择的特征，与犬型分支的TfR和细小病毒之间的进化军备竞赛一致。除了修饰结合的氨基酸序列的修饰外，我们还发现狗的TfR中的糖基化位点突变提供了对大约1975年之前循环的食肉动物细小病毒的抗性，该突变早于土狼和狗的物种形成。由于与它们关系密切的黑背豺有一个类似于它们共同祖先的TfR，并且缺乏糖基化位点，因此将这种突变重建到豺TfR中显示了该位点在阻断结合和感染方面的效力，并解释了直到最近狗的抗性。这改变了我们对这个众所周知的病毒出现例子的理解，表明犬细小病毒的出现可能是由于细小病毒对前宿主的抗性受体的重新适应。猫和狗中的细小病毒已被研究为模型系统，以了解病毒如何获得感染新宿主物种的能力。通过研究转铁蛋白受体的进化，病毒利用转铁蛋白受体进入细胞，我们发现狗的祖先可能在数百万年前被细小病毒感染，直到它们进化并具有抵抗力;这是由于它们的转铁蛋白受体发生变化，因此它不再与病毒结合。当一种感染狗的变异病毒在20世纪70年代出现时，它已经适应了克服这一障碍。这个故事表明，曾经从一个物种中消失的疾病可以进化并重新获得对该宿主的感染力，因此具有很高的新兴疾病的可能性。我们确定了对宿主-病毒相互作用的演变很重要的受体特征，并证实了它们在细胞培养中调节病毒结合的作用。
Parvoviruses exploit transferrin receptor type-1 (TfR) for cellular entry in carnivores, and specific interactions are key to control of host range. We show that several key mutations acquired by TfR during the evolution of Caniforms (dogs and related species) modified the interactions with parvovirus capsids by reducing the level of binding. These data, along with signatures of positive selection in the TFRC gene, are consistent with an evolutionary arms race between the TfR of the Caniform clade and parvoviruses. As well as the modifications of amino acid sequence which modify binding, we found that a glycosylation site mutation in the TfR of dogs which provided resistance to the carnivore parvoviruses which were in circulation prior to about 1975 predates the speciation of coyotes and dogs. Because the closely-related black-backed jackal has a TfR similar to their common ancestor and lacks the glycosylation site, reconstructing this mutation into the jackal TfR shows the potency of that site in blocking binding and infection and explains the resistance of dogs until recent times. This alters our understanding of this well-known example of viral emergence by indicating that canine parvovirus emergence likely resulted from the re-adaptation of a parvovirus to the resistant receptor of a former host. Parvoviruses in cats and dogs have been studied as a model system to understand how viruses gain the ability to infect new host species. By studying the evolution of the transferrin receptor, which the virus uses to enter a cell, we discovered that the ancestors of dogs were likely infected by a parvovirus millions of years ago until they evolved and became resistant; this was caused by their transferrin receptor changing so it no longer bound the virus. When a variant virus that infects dogs emerged in the 1970s, it had adapted to overcome this block. This story suggests that diseases which were once eliminated from a species can evolve and regain the infectivity for that host, therefore having high potential to be emerging diseases. We identified features of the receptor that were important to the evolution of this host-virus interaction and confirmed their role in regulating virus binding in cell culture.
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影响因子：
15.9
作者：
Meyerson NR;Sawyer SL
通讯作者：
Sawyer SL
影响因子：
56.9
作者：
Lawrence, CM;Ray, S;Harrison, SC
通讯作者：
Harrison, SC
影响因子：
64.5
作者：
Lebrón, JA;Bennett, MJ;Bjorkman, PJ
通讯作者：
Bjorkman, PJ
DOI：
10.1099/vir.0.2008/002055-0
发表时间：
2008-09
期刊：
The Journal of general virology
影响因子：
--
作者：
Hoelzer K;Shackelton LA;Parrish CR;Holmes EC
通讯作者：
Holmes EC
影响因子：
5.4
作者：
Kapoor, Amit;Simmonds, Peter;Lipkin, W. Ian
通讯作者：
Lipkin, W. Ian