Case-Control Comparison of Enteric Viromes in Captive Rhesus Macaques with Acute or Idiopathic Chronic Diarrhea

Abstract

Diarrhea is the major cause of non-research-associated morbidity and mortality affecting the supply of rhesus macaques and, potentially, their responses to experimental treatments. Idiopathic chronic diarrhea (ICD) in rhesus macaques also resembles ulcerative colitis, one form of human inflammatory bowel disease. To test for viral etiologies, we characterized and compared the fecal viromes from 32 healthy animals, 31 animals with acute diarrhea, and 29 animals with ICD. The overall fractions of eukaryotic viral reads were 0.063% for the healthy group, 0.131% for the acute-diarrhea group, and 0.297% for the chronic-diarrhea group. Eukaryotic viruses belonging to 6 viral families, as well as numerous circular Rep-encoding singlestranded DNA (CRESS DNA) viral genomes, were identified. The most commonly detected sequences were from picornaviruses, making up 59 to 88% of all viral reads, followed by 9 to 17% for CRESS DNA virus sequences. The remaining 5 virus families, Adenoviridae, Astroviridae, Anelloviridae, Picobirnaviridae, and Parvoviridae, collectively made up 1 to 3% of the viral reads, except for parvoviruses, which made up 23% of the viral reads in the healthy group. Detected members of the families Picornaviridae and Parvoviridae were highly diverse, consisting of multiple genera, species, and genotypes. Coinfections with members of up to six viral families were detected. Complete and partial viral genomes were assembled and used to measure the number of matching short sequence reads in feces from the 92 animals in the two clinical and the healthy control groups. Several enterovirus genotypes and CRESS DNA genomes were associated with ICD relative to healthy animals. Conversely, higher read numbers from different parvoviruses were associated with healthy animals. Our study reveals a high level of enteric coinfections with diverse viruses in a captive rhesus macaque colony and identifies several viruses positively or negatively associated with ICD.KEYWORDS enterovirus, sapelovirus, parvovirus, CRESS-DNA, idiopathic diarrhea, rhesus macaques, enteric disease etiology W e compared the enteric viromes of captive rhesus macaques (Macaca mulatta) with acute and idiopathic chronic diarrhea (ICD) to those of healthy animals using a case-control study. The genomes of several known and new viruses were characterized using metagenomics. We showed that some specific enterovirus genotypes and some small circular DNA genomes are associated with chronic idiopathic diarrhea, providing candidates for further testing of their pathogenicity. Other viruses, including some parvoviruses, were found at significantly higher levels in healthy animals.

Plasma virome of 781 Brazilians with unexplained symptoms of arbovirus infection include a novel parvovirus and densovirus

“…These viruses belong either to a viral clade known to infect vertebrates but not previously reported in human (chapparvovirus) or known to infect invertebrates but not vertebrate hosts (ambidensovirus). Diverse chapparvovirus genomes, fecally shed by non-human mammals, including rhesus macaques [42] and…”

Virus discovery in all three major lineages of terrestrial arthropods highlights the diversity of single-stranded DNA viruses associated with invertebrates

“…Since then, metagenomic studies have revealed the cosmopolitan and diverse nature of eukaryotic CRESS DNA viruses. CRESS DNA viruses have now been reported from a wide array of organisms, ranging from primates (e.g., Kapusinszky et al 2017;Ng et al 2015) to unicellular algae (Yoon et al 2011), and ecosystems spanning aquatic (e.g., Labonté and Suttle 2013;Lopez-Bueno et al 2009;Dayaram, Goldstien, et al 2015;Hewson, Eaglesham, et al 2013), terrestrial (e.g., Reavy et al 2015;Kim et al 2008), airborne (e.g., Whon et al 2012) and man-made environments (e.g. Kraberger et al 2015;Rosario, Duffy, and Breitbart 2009;Rosario et al 2018).…”

“…Porprismacovirus is by far the genus with the highest number of species in the family(Varsani and Krupovic 2018). Although both FlyACV-3 and -4 represent new species, FlyACV-3 is closely related to an unclassified smacovirus isolated from macaque feces(Kapusinszky et al 2017). Therefore, FlyACV-3 and the unclassified macaque associated smacovirus represent variants of the same Porprismacovirus species.…”

Peer Review #2 of "Virus discovery in all three major lineages of terrestrial arthropods highlights the diversity of single-stranded DNA viruses associated with invertebrates (v0.1)"

“…Since then, metagenomic studies have revealed the cosmopolitan and diverse nature of eukaryotic CRESS DNA viruses. CRESS DNA viruses have now been reported from a wide array of organisms, ranging from primates (e.g., Kapusinszky et al 2017;Ng et al 2015) to unicellular algae (Yoon et al 2011), and ecosystems spanning aquatic (e.g., Dayaram et al 2015a;Hewson et al 2013a;Labonté & Suttle 2013;Lopez-Bueno et al 2009), terrestrial (e.g., Kim et al 2008;Reavy et al 2015), airborne (e.g., Whon et al 2012) and man-made environments (e.g., Kraberger et al 2015;Rosario et al 2009;Rosario et al 2018). The increased detection and expanded diversity of CRESS DNA viruses has resulted in the establishment of four new taxonomic groups by the International Committee for the Taxonomy of Viruses (ICTV), including three new families (Genomoviridae, Smacoviridae, Bacilladnaviridae) PeerJ reviewing PDF | (2018:08:30117:1:1:NEW 10 Sep 2018)…”