M'Bana Viriato, Lahree Aparajita, Marques Sofia, Slavic Ksenija, Mota Maria M
Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal.
Pós-graduação Ciência para o Desenvolvimento, Portugal.
iScience. 2022 Apr 22;25(5):104281. doi: 10.1016/j.isci.2022.104281. eCollection 2022 May 20.
Parasite-derived PVM-resident proteins are critical for complete parasite development inside hepatocytes, although the function of most of these proteins remains unknown. Here, we show that the upregulated in infectious sporozoites 4 (UIS4) protein, resident at the PVM, interacts with the host cell actin. By suppressing filamentous actin formation, UIS4 avoids parasite elimination. Host cell actin dynamics increases around UIS4-deficient parasites, which is associated with subsequent parasite elimination. Notably, parasite elimination is impaired significantly by the inhibition of host myosin-II, possibly through relieving the compression generated by actomyosin complexes at the host-parasite interface. Together, these data reveal that UIS4 has a critical role in the evasion of host defensive mechanisms, enabling hence EEF survival and development.
寄生虫来源的寄生泡膜驻留蛋白对于寄生虫在肝细胞内的完全发育至关重要，尽管这些蛋白中大多数的功能仍不清楚。在此，我们表明驻留在寄生泡膜的感染性子孢子上调蛋白4（UIS4）与宿主细胞肌动蛋白相互作用。通过抑制丝状肌动蛋白的形成，UIS4避免寄生虫被清除。在缺乏UIS4的寄生虫周围，宿主细胞肌动蛋白动力学增加，这与随后的寄生虫清除有关。值得注意的是，宿主肌球蛋白-II的抑制显著损害了寄生虫的清除，这可能是通过减轻肌动球蛋白复合物在宿主-寄生虫界面产生的压缩力来实现的。总之，这些数据表明UIS4在逃避宿主防御机制中起关键作用，从而使肝内期疟原虫得以存活和发育。
