Petrone Mary E, Charon Justine, Grigg Matthew J, William Timothy, Rajahram Giri S, Westaway Jacob, Piera Kim A, Shi Mang, Anstey Nicholas M, Holmes Edward C
Sydney Institute for Infectious Diseases, School of Medical Sciences, The University of Sydney, Sydney, NSW 2006, Australia.
Laboratory of Data Discovery for Health Limited, Hong Kong SAR, China.
bioRxiv. 2024 Sep 19:2024.09.18.613759. doi: 10.1101/2024.09.18.613759.
Apicomplexa are single-celled eukaryotes that can infect humans and include the mosquito-borne parasite , the cause of malaria. Increasing rates of drug resistance in human-only species are reducing the efficacy of control efforts and antimalarial treatments. There are also rising cases of , the only zoonotic species that causes severe disease and death in humans. Thus, there is a need to develop additional innovative strategies to combat malaria. Viruses that infect non- spp. Disease-causing protozoa have been shown to affect pathogen life cycle and disease outcomes. However, only one virus (Matryoshka RNA virus 1) has been identified in , and none have been identified in zoonotic species. The rapid expansion of the known RNA virosphere using structure- and artificial intelligence-based methods suggests that this dearth is due to the divergent nature of RNA viruses that infect protozoa. We leveraged these newly uncovered data sets to explore the virome of human-infecting species collected in Sabah, east (Borneo) Malaysia. We identified a highly divergent RNA virus in two human-infecting isolates that is related to the unclassified group 'ormycoviruses'. By characterising fifteen additional ormycoviruses identified in the transcriptomes of arthropods we show that this group of viruses exhibits a complex ecology at the arthropod-mammal interface. Through the application of artificial intelligence methods, we then demonstrate that the ormycoviruses are part of a diverse and unclassified viral taxon. This is the first observation of an RNA virus in a zoonotic species. By linking small-scale experimental data to large-scale virus discovery advances, we characterise the diversity and genomic architecture of an unclassified viral taxon. This approach should be used to further explore the virome of disease-causing Apicomplexa and better understand how protozoa-infecting viruses may affect parasite fitness, pathobiology, and treatment outcomes.
顶复门原虫是可感染人类的单细胞真核生物,包括通过蚊子传播的寄生虫,即疟疾的病原体。仅感染人类的疟原虫物种中耐药率不断上升,正在降低防控措施和抗疟治疗的效果。同时,人兽共患疟原虫物种导致人类严重疾病和死亡的病例也在增加。因此,需要制定更多创新策略来对抗疟疾。已证明感染非疟原虫物种的致病原生动物的病毒会影响病原体的生命周期和疾病结局。然而,在疟原虫中仅鉴定出一种病毒(套娃RNA病毒1),而在人兽共患疟原虫物种中尚未鉴定出任何病毒。利用基于结构和人工智能的方法对已知RNA病毒圈的快速扩展表明,这种缺乏是由于感染原生动物的RNA病毒具有多样性。我们利用这些新发现的数据集来探索在马来西亚东部(婆罗洲)沙巴收集的感染人类的疟原虫物种的病毒组。我们在两种感染人类的疟原虫分离株中鉴定出一种高度分化的RNA病毒,它与未分类的“卵菌病毒”组有关。通过对在节肢动物转录组中鉴定出的另外15种卵菌病毒进行表征,我们表明这组病毒在节肢动物 - 哺乳动物界面表现出复杂的生态。通过应用人工智能方法,我们随后证明卵菌病毒是一个多样且未分类的病毒分类群的一部分。这是在人兽共患疟原虫物种中首次观察到RNA病毒。通过将小规模实验数据与大规模病毒发现进展联系起来,我们表征了一个未分类病毒分类群的多样性和基因组结构。这种方法应用于进一步探索致病顶复门原虫的病毒组,并更好地了解感染原生动物的病毒如何影响寄生虫适应性、病理生物学和治疗结果。