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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.
Metagenomics allows virus genome discovery, but the viral hosts are often not identified. Here, Kinsella et al. use recombination events between virus genomes, statistical association of viruses to hosts in clinical samples, and analysis of endogenous viral elements in host genomes to identify probable hosts of three CRESS virus families.
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1 Amsterdam UMC, University of Amsterdam, Laboratory of Experimental Virology, Department of Medical Microbiology and Infection Prevention, Amsterdam, The Netherlands (GRID:grid.7177.6) (ISNI:0000000084992262)
2 Amsterdam UMC, University of Amsterdam, Laboratory of Clinical Parasitology, Department of Medical Microbiology and Infection Prevention, Amsterdam, The Netherlands (GRID:grid.7177.6) (ISNI:0000000084992262)
3 MRC/UVRI & LSHTM Uganda Research Unit, Entebbe, Uganda (GRID:grid.7177.6); MRC-University of Glasgow Centre for Virus Research, Glasgow, UK (GRID:grid.301713.7) (ISNI:0000 0004 0393 3981)