控制野生来源小鼠中毒力强的弓形虫感染的分子机制。

Molecular mechanism for the control of virulent Toxoplasma gondii infections in wild-derived mice.

机构信息

Institute of Virology, Medical Center University of Freiburg, 79104, Freiburg, Germany.

Faculty of Medicine, University of Freiburg, 79104, Freiburg, Germany.

出版信息

Nat Commun. 2019 Mar 15;10(1):1233. doi: 10.1038/s41467-019-09200-2.

Some strains of the protozoan parasite Toxoplasma gondii (such as RH) are virulent in laboratory mice because they are not restricted by the Immunity-Related GTPase (IRG) resistance system in these mouse strains. In some wild-derived Eurasian mice (such as CIM) on the other hand, polymorphic IRG proteins inhibit the replication of such virulent T. gondii strains. Here we show that this resistance is due to direct binding of the IRG protein Irgb2-b1 to the T. gondii virulence effector ROP5 isoform B. The Irgb2-b1 interface of this interaction is highly polymorphic and under positive selection. South American T. gondii strains are virulent even in wild-derived Eurasian mice. We were able to demonstrate that this difference in virulence is due to polymorphic ROP5 isoforms that are not targeted by Irgb2-b1, indicating co-adaptation of host cell resistance GTPases and T. gondii virulence effectors.

有些刚地弓形虫（Toxoplasma gondii）原虫寄生虫的菌株（如 RH）在实验室小鼠中具有毒力，因为它们不受这些小鼠品系中免疫相关 GTP 酶（IRG）抵抗系统的限制。另一方面，在一些来自欧亚大陆的野生来源的小鼠（如 CIM）中，多态性的 IRG 蛋白抑制了这种毒力 T. gondii 菌株的复制。在这里，我们表明这种抗性是由于 IRG 蛋白 Irgb2-b1 与 T. gondii 毒力效应蛋白 ROP5 亚型 B 的直接结合所致。这种相互作用的 Irgb2-b1 界面高度多态，并且受到正选择。南美洲的 T. gondii 菌株即使在来自欧亚大陆的野生来源的小鼠中也是毒力的。我们能够证明这种毒力差异是由于多态性的 ROP5 亚型引起的，这些亚型不受 Irgb2-b1 的靶向，表明宿主细胞抗性 GTPases 和 T. gondii 毒力效应蛋白的共同适应。