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首页> 外文期刊>Infection and immunity >Targeted Disruption of the GRA2 Locus inToxoplasma gondii Decreases Acute Virulence in Mice
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Targeted Disruption of the GRA2 Locus inToxoplasma gondii Decreases Acute Virulence in Mice

机译：弓形虫弓形虫中的GRA2基因座的靶向破坏降低了小鼠的急性毒力。

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Following invasion into the host cell, the protozoanToxoplasma gondii secretes a variety of proteins that modify the parasitophorous vacuole. Within the vacuole, the 28-kDa dense granule protein known as GRA2 is specifically targeted to the tubulovesicular network which forms connections with the vacuolar membrane. To investigate the importance of GRA2, we derived from strain RH a mutant T. gondii line in which GRA2 was disrupted by replacement with the marker Ble (selecting for phleomycin resistance). The Δgra2 mutant invaded and grew normally in both fibroblasts and macrophages in vitro; however, it was less virulent during acute infection in mice. The survival rate of mice inoculated with Δgra2 was significantly higher; some infected mice survived the acute infection, whereas all mice infected with the wild-type strain RH succumbed to early death. Chronic infection by Δgra2 was detected by positive serology, immunohistochemical detection of parasites and cysts in the brain, and reisolation of parasites by bioassay at 6 weeks postinfection. Thus, absence of GRA2 partially attenuates the virulence of T. gondii during the acute phase of infection and allows for establishment of chronic infection by the otherwise highly virulent RH strain. These results establish that GRA2 plays an important role during in vivo infection and provide a potential model for examining acute pathogenesis by T. gondii.
机译：入侵宿主细胞后，原生动物<弓形虫>弓形虫分泌出多种蛋白质，修饰了寄生虫的液泡。在液泡内，称为GRA2的28 kDa致密颗粒蛋白专门靶向微管网状体网络，该网络与液泡膜形成连接。为了研究GRA2的重要性，我们从RH菌株中衍生了一个突变体 T。标记为Ble的Gondii 品系，其中的 GRA2 被破坏（选择了抗霉素）。 Δ gra2 突变体在成纤维细胞和巨噬细胞中均能侵入并正常生长。但是，它在小鼠急性感染过程中的毒性较小。接种了 gra2 的小鼠的存活率明显更高;一些被感染的小鼠在急性感染中幸存下来，而所有被野生型RH感染的小鼠都死于早期死亡。阳性血清学，免疫组织化学检测脑中的寄生虫和囊肿以及感染后6周通过生物测定重新分离出寄生虫，从而检测到Δ gra2 的慢性感染。因此，不存在GRA2会部分减弱 T的毒力。刚体在感染的急性期，可以通过其他高毒力的RH株建立慢性感染。这些结果表明，GRA2在体内感染过程中起着重要作用，并为通过 T检查急性发病机制提供了潜在的模型。刚地。

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