A Parasite Odyssey: An RNA virus concealed inToxoplasma gondii

Abstract

We are in the midst of the "Platinum Age of Virus Discovery", an era characterized by the exponential growth in the discovery of virus biodiversity. In humans (or any animal) there are more viruses than simply those directly infecting the animal cells. Viruses infect all species 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 network we must employ computationally assisted virology as a means of analyzing and interpreting the millions of available samples to decipher the myriad of ways in which viruses may intersect human health. From a global screen for human neuron-associated viruses, we identify a novel narnavirus Achaeavirus odysseus (Ao) which likely infects the neurotropic parasite Toxoplasma gondii. Previously, several parasitic protozoan viruses (PPVs) have been mechanistically established as triggers of host innate responses, and here we present in silico evidence that Ao is a plausible pro-inflammatory factor in mouse and human cells infected by T. gondii. T. gondii 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. More broadly, we explore phylogenetically proximal viruses to Ao and discover 18 new species of Achaeavirus, all found in vertebrate transcriptome and metatranscriptomes. While the Narnavirus samples making up this genus-like clade are derived from sheep, goat, bat, rabbit, chicken, and pigeon, the presence of virus is strongly predictive of parasitic (Apicomplexa) nucleic acid co-occurrence, supporting that these are a clade of parasite-infecting viruses. This is a computational proof-of-concept study in which we rapidly analyze millions of datasets from which we distill a mechanistically, ecologically, and phylogenetically refined hypothesis. We predict this highly diverged Ao RNA virus is biologically a T. gondii infection, and that Ao, and other viruses like it, will modulate this disease which afflicts billions worldwide.