Gupta Purav, Hiller Aiden, Chowdhury Jawad, Lim Declan, Lim Dillon Yee, Saeij Jeroen P J, Babaian Artem, Rodriguez Felipe, Pereira Luke, Morales-Tapia Alejandro
The Woodlands Secondary School, 3225 Erindale Station Rd,Mississauga, ON L5C 1Y5, Canada.
Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
Virus Evol. 2024 May 11;10(1):veae040. doi: 10.1093/ve/veae040. eCollection 2024.
We are entering a 'Platinum Age of Virus Discovery', an era marked by exponential growth in the discovery of virus biodiversity, and driven by advances in metagenomics and computational analysis. In the ecosystem of a human (or any animal) there are more species of viruses than simply those directly infecting the animal cells. Viruses can infect all organisms constituting the microbiome, including bacteria, fungi, and unicellular parasites. Thus the complexity of possible interactions between host, microbe, and viruses is unfathomable. To understand this interaction network we must employ computationally assisted virology as a means of analyzing and interpreting the millions of available samples to make inferences about the ways in which viruses may intersect human health. From a computational viral screen of human neuronal datasets, we identified a novel narnavirus (Ao) which likely infects the neurotropic parasite . Previously, several parasitic protozoan viruses (PPVs) have been mechanistically established as triggers of host innate responses, and here we present evidence that Ao is a plausible pro-inflammatory factor in human and mouse cells infected by infects billions of people worldwide, yet the prognosis of toxoplasmosis disease is highly variable, and PPVs like Ao could function as a hitherto undescribed hypervirulence factor. In a broader screen of over 7.6 million samples, we explored phylogenetically proximal viruses to Ao and discovered nineteen species, all found in libraries annotated as vertebrate transcriptome or metatranscriptomes. While samples containing this genus of narnaviruses are derived from sheep, goat, bat, rabbit, chicken, and pigeon samples, the presence of virus is strongly predictive of parasitic nucleic acid co-occurrence, supporting the fact that is a genus of parasite-infecting viruses. This is a computational proof-of-concept study in which we rapidly analyze millions of datasets from which we distilled a mechanistically, ecologically, and phylogenetically refined hypothesis. We predict that this highly diverged Ao RNA virus is biologically a infection, and that Ao, and other viruses like it, will modulate this disease which afflicts billions worldwide.
我们正在进入一个“病毒发现的白金时代”,这是一个以病毒生物多样性发现呈指数级增长为标志的时代,由宏基因组学和计算分析的进展所驱动。在人类(或任何动物)的生态系统中,病毒的种类不仅仅是那些直接感染动物细胞的病毒。病毒可以感染构成微生物群的所有生物体,包括细菌、真菌和单细胞寄生虫。因此,宿主、微生物和病毒之间可能的相互作用的复杂性是难以想象的。为了理解这个相互作用网络,我们必须采用计算辅助病毒学作为分析和解释数百万可用样本的手段,以便推断病毒可能与人类健康交叉的方式。通过对人类神经元数据集的计算病毒筛选,我们鉴定出一种新型的纳罗病毒(Ao),它可能感染嗜神经寄生虫。以前,几种寄生原生动物病毒(PPV)已被机械地确定为宿主先天反应的触发因素,在这里我们提供证据表明,Ao在被弓形虫感染的人类和小鼠细胞中是一种合理的促炎因子。弓形虫感染全球数十亿人,然而弓形虫病的预后差异很大,像Ao这样的PPV可能作为一种迄今未被描述的高毒力因子发挥作用。在对超过760万个样本的更广泛筛选中,我们探索了与Ao系统发育上接近的病毒,发现了19个物种,所有这些物种都在注释为脊椎动物转录组或元转录组的文库中发现。虽然含有这种纳罗病毒属的样本来自绵羊、山羊、蝙蝠、兔子、鸡和鸽子的样本,但病毒的存在强烈预示着寄生虫核酸的共现,支持了该病毒是一类感染寄生虫的病毒这一事实。这是一项计算概念验证研究,我们在其中快速分析了数百万个数据集,并从中提炼出一个在机制、生态和系统发育上经过完善的假设。我们预测,这种高度分化的Ao RNA病毒在生物学上是弓形虫感染的调节剂,并且Ao以及其他类似的病毒将调节这种困扰全球数十亿人的疾病。