Characterization of the Tubovesicular Network in Plasmodium vivax Liver Stage Hypnozoites and Schizonts.
Characterization of the Tubovesicular Network in Plasmodium vivax Liver Stage Hypnozoites and Schizonts.
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DOI：
10.3389/fcimb.2021.687019
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发表时间：
2021
影响因子：
5.7
通讯作者：
Derbyshire ER
中科院分区：
文献类型：
--
作者：
Sylvester K;Maher SP;Posfai D;Tran MK;Crawford MC;Vantaux A;Witkowski B;Kyle DE;Derbyshire ER
疟原虫是顶复合体寄生虫的一个属，在引起疟疾之前在肝脏中复制。间日疟原虫也可以作为休眠的催眠虫在肝脏中持续存在，激活后引起临床复发，但导致激活的分子机制尚未发现。在这项研究中，我们使用高分辨率显微镜来表征间日疟原虫肝期管泡网络（TVN）的时间变化，这是宿主细胞质内寄生液泡膜（PVM）衍生的网络。我们观察到延伸的膜簇、小管和tvn衍生的囊泡存在于间日疟原虫肝脏发育阶段。此外，我们在催眠子中发现了意想不到的TVN，并观察到该网络与宿主核的一些关联。我们还揭示了宿主水和溶质通道水通道蛋白-3 （AQP3）与tvn衍生的囊泡和扩展膜团簇有关。AQP3先前已被证明定位于间日疟原虫催眠子和肝分裂体的PVM，但尚未显示与TVN相关。我们的研究结果强调宿主-寄生虫相互作用发生在休眠和复制肝期间日疟原虫中，并在此期间影响AQP3功能。总之，这些发现增强了我们对间日疟原虫肝期生物学的理解，通过对TVN的表征，强调了该网络在休眠催眠虫中的存在。
Plasmodium is a genus of apicomplexan parasites which replicate in the liver before causing malaria. Plasmodium vivax can also persist in the liver as dormant hypnozoites and cause clinical relapse upon activation, but the molecular mechanisms leading to activation have yet to be discovered. In this study, we use high-resolution microscopy to characterize temporal changes of the P. vivax liver stage tubovesicular network (TVN), a parasitophorous vacuole membrane (PVM)-derived network within the host cytosol. We observe extended membrane clusters, tubules, and TVN-derived vesicles present throughout P. vivax liver stage development. Additionally, we demonstrate an unexpected presence of the TVN in hypnozoites and observe some association of this network to host nuclei. We also reveal that the host water and solute channel aquaporin-3 (AQP3) associates with TVN-derived vesicles and extended membrane clusters. AQP3 has been previously shown to localize to the PVM of P. vivax hypnozoites and liver schizonts but has not yet been shown in association to the TVN. Our results highlight host-parasite interactions occur in both dormant and replicating liver stage P. vivax forms and implicate AQP3 function during this time. Together, these findings enhance our understanding of P. vivax liver stage biology through characterization of the TVN with an emphasis on the presence of this network in dormant hypnozoites.