Abstract
Metagenomic techniques have enabled genome sequencing of unknown viruses without isolation in cell culture, but information on the virus host is often lacking, preventing viral characterisation. High-throughput methods capable of identifying virus hosts based on genomic data alone would aid evaluation of their medical or biological relevance. Here, we address this by linking metagenomic discovery of three virus families in human stool samples with determination of probable hosts. Recombination between viruses provides evidence of a shared host, in which genetic exchange occurs. We utilise networks of viral recombination to delimit virus-host clusters, which are then anchored to specific hosts using (1) statistical association to a host organism in clinical samples, (2) endogenous viral elements in host genomes, and (3) evidence of host small RNA responses to these elements. This analysis suggests two CRESS virus families (Naryaviridae and Nenyaviridae) infect Entamoeba parasites, while a third (Vilyaviridae) infects Giardia duodenalis. The trio supplements five CRESS virus families already known to infect eukaryotes, extending the CRESS virus host range to protozoa. Phylogenetic analysis implies CRESS viruses infecting multicellular life have evolved independently on at least three occasions.
Highlights
Metagenomic techniques have enabled genome sequencing of unknown viruses without isolation in cell culture, but information on the virus host is often lacking, preventing viral characterisation
Searches for endogenous viral elements related to CRESS viruses have revealed integrations into the genomes of eukaryotes, for instance, sequences related to the replication-associated protein (Rep) of Geminiviridae, major global crop pathogens, are integrated in the tobacco genome[22]
Rep-like sequences are found in the genomes of the protozoan gut parasites Entamoeba histolytica and Giardia duodenalis[23], important human pathogens belonging to distantly related genera[24]
Summary
Metagenomic techniques have enabled genome sequencing of unknown viruses without isolation in cell culture, but information on the virus host is often lacking, preventing viral characterisation. High-throughput methods capable of identifying virus hosts based on genomic data alone would aid evaluation of their medical or biological relevance We address this by linking metagenomic discovery of three virus families in human stool samples with determination of probable hosts. We utilise networks of viral recombination to delimit virus-host clusters, which are anchored to specific hosts using (1) statistical association to a host organism in clinical samples, (2) endogenous viral elements in host genomes, and (3) evidence of host small RNA responses to these elements This analysis suggests two CRESS virus families (Naryaviridae and Nenyaviridae) infect Entamoeba parasites, while a third (Vilyaviridae) infects Giardia duodenalis. Virus–host relationships are determined via recognition of host disease, followed by virus isolation in cell culture Since this is impractical for metagenomically identified viruses, case-control studies are used to reveal associations between viruses and disease.
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