Giant viruses (Nucleocytoviricota) are significant lethality agents of various eukaryotic hosts. Although metagenomics indicates their ubiquitous distribution, available giant virus isolates are restricted to a very small number of protist and algal hosts. Here we report on the first viral isolate that replicates in the amoeboflagellate Naegleria. This genus comprises the notorious human pathogen Naegleria fowleri, the causative agent of the rare but fatal primary amoebic meningoencephalitis. We have elucidated the structure and infection cycle of this giant virus, Catovirus naegleriensis (a.k.a. Naegleriavirus, NiV), and show its unique adaptations to its Naegleria host using fluorescence in situ hybridization, electron microscopy, genomics, and proteomics. Naegleriavirus is only the fourth isolate of the highly diverse subfamily Klosneuvirinae, and like its relatives the NiV genome contains a large number of translation genes, but lacks transfer RNAs (tRNAs). NiV has acquired genes from its Naegleria host, which code for heat shock proteins and apoptosis inhibiting factors, presumably for host interactions. Notably, NiV infection was lethal to all Naegleria species tested, including the human pathogen N. fowleri. This study expands our experimental framework for investigating giant viruses and may help to better understand the basic biology of the human pathogen N. fowleri.

巨型病毒（核细胞病毒）是各种真核宿主的重要致死剂。尽管宏基因组学表明它们分布广泛，但可用的巨型病毒分离株仅限于极少数原生生物和藻类宿主。在这里，我们报告了第一个在变形虫鞭毛虫内复制的病毒分离株。该属包括臭名昭著的人类病原体福氏耐格里阿米巴原虫，它是罕见但致命的原发性阿米巴脑膜脑炎的病原体。我们阐明了这种巨型病毒——卡托病毒内格勒病毒（又名内格勒病毒，NiV）的结构和感染周期，并利用荧光原位杂交、电子显微镜、基因组学和蛋白质组学展示了其对其宿主内格勒病毒的独特适应。耐格里病毒只是高度多样化的克洛斯新病毒亚科的第四个分离株，与它的近亲一样，NiV 基因组包含大量翻译基因，但缺乏转移 RNA (tRNA)。 NiV 从其耐格里阿米巴属宿主那里获得了基因，这些基因编码热休克蛋白和细胞凋亡抑制因子，可能与宿主相互作用有关。值得注意的是，NiV 感染对所有测试的耐格里阿米巴属物种都是致命的，包括人类病原体福氏耐格里阿米巴。这项研究扩展了我们研究巨型病毒的实验框架，并可能有助于更好地了解人类病原体福氏奈瑟菌的基本生物学。