Abstract:
Endogenous viral elements (EVEs) are common genetic passengers in various protists. Some EVEs represent viral fossils, whereas others are still active. The marine heterotrophic flagellate Cafeteria burkhardae contains several EVE types related to the virophage mavirus, a small DNA virus that parasitizes the lytic giant virus CroV. We hypothesized that endogenous virophages may act as an antiviral defense system in protists, but no protective effect of virophages in wild host populations has been shown so far. Here, we tested the activity of virophage EVEs and studied their impact on giant virus replication. We found that endogenous mavirus-like elements (EMALEs) from globally distributed Cafeteria populations produced infectious virus particles specifically in response to CroV infection. However, reactivation was stochastic, often inefficient, and poorly reproducible. Interestingly, only one of eight EMALE types responded to CroV infection, implying that other EMALEs may be linked to different giant viruses. We isolated and cloned several reactivated virophages and characterized their particles, genomes, and infection dynamics. All tested virophages inhibited the production of CroV during coinfection, thereby preventing lysis of the host cultures in a dose-dependent manner. Comparative genomics of different C. burkhardae strains revealed that inducible EMALEs are common and are not linked to specific geographic locations. We demonstrate that naturally occurring virophage EVEs reactivate upon giant virus infection, thus providing a striking example that eukaryotic EVEs can become active under specific conditions. Moreover, our results support the hypothesis that virophages can act as an adaptive antiviral defense system in protists.
摘要:
内源性病毒元件(EVE)是各种原生生物中常见的遗传乘客。有些EVE代表病毒化石,而其他人仍然活跃。海洋异养鞭毛虫Cafeteriaburkhardae包含几种与病毒有关的EVE类型,一种小的DNA病毒,寄生在裂解巨型病毒CroV上。我们假设内源性病毒可能在原生生物中充当抗病毒防御系统,但是到目前为止,还没有显示出野生寄主种群中病毒的保护作用。这里,我们测试了病毒体EVE的活性,并研究了它们对巨型病毒复制的影响。我们发现,来自全球分布的自助餐厅种群的内源性马氏病毒样元件(EMALE)产生了特异性响应于CroV感染的感染性病毒颗粒。然而,再激活是随机的,通常效率低下,和可重复性差。有趣的是,八种EMAE类型中只有一种对CroV感染有反应,暗示其他EMALE可能与不同的巨型病毒有关。我们分离并克隆了几种重新激活的病毒,并表征了它们的颗粒,基因组,和感染动力学。所有测试的病毒在共感染期间抑制了CroV的产生,从而以剂量依赖性方式防止宿主培养物的裂解。不同C.burkhardae菌株的比较基因组学表明,诱导型EMALE是常见的,并且与特定的地理位置无关。我们证明,自然发生的病毒EVE在巨大病毒感染后会重新激活,因此提供了一个引人注目的例子,真核EVE可以在特定条件下变得活跃。此外,我们的结果支持这一假设,即病毒可以在原生生物中充当适应性抗病毒防御系统。