A diverse group of small circular ssDNA viral genomes in human and non-human primate stools

Abstract

Viral metagenomics sequencing of fecal samples from outbreaks of acute gastroenteritis from the US revealed the presence of small circular ssDNA viral genomes encoding a replication initiator protein (Rep). Viral genomes were ∼2.5 kb in length, with bi-directionally oriented Rep and capsid (Cap) encoding genes and a stem loop structure downstream of Rep. Several genomes showed evidence of recombination. By digital screening of an in-house virome database (1.04 billion reads) using BLAST, we identified closely related sequences from cases of unexplained diarrhea in France. Deep sequencing and PCR detected such genomes in 7 of 25 US (28 percent) and 14 of 21 French outbreaks (67 percent). One of eighty-five sporadic diarrhea cases in the Gambia was positive by PCR. Twenty-two complete genomes were characterized showing that viruses from patients in the same outbreaks were closely related suggesting common origins. Similar genomes were also characterized from the stools of captive chimpanzees, a gorilla, a black howler monkey, and a lemur that were more diverse than the human stool-associated genomes. The name smacovirus is proposed for this monophyletic viral clade. Possible tropism include mammalian enteric cells or ingested food components such as infected plants. No evidence of viral amplification was found in immunodeficient mice orally inoculated with smacovirus-positive stool supernatants. A role for smacoviruses in diarrhea, if any, remains to be demonstrated.

Smacoviridae: a new family of animal-associated single-stranded DNA viruses

“…Smacoviruses [15,17], previously also referred to as chipoviruses [22,24], have been identified in faecal matter of various vertebrates, including humans, as well as in the abdomina of dragonflies of two species (Table 1). Thus far, none of these viruses have been cultured or found in animal tissue sample.…”

“…Thus far, none of these viruses have been cultured or found in animal tissue sample. Nonetheless, the viruses have been discovered using viral metagenomics approaches and for the majority of the smacoviruses, the validity of genome sequences has been verified by either PCR amplification using abutting primers followed by Sanger sequencing of these products or by amplification, cloning and Sanger sequencing of the recombinant plasmids [1,3,4,9,15,22,24]. Camel associated porprismacovirus 1…”

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

“…1). While the tropism of some CRESS DNA viruses, such as circoviruses (infecting vertebrates) and geminivirus (infecting plants), has been clearly defined, the large majority of such genomes have been characterized using metagenomics from environmental or nonsterile samples, such as feces (13,24,26,35,(62)(63)(64)(65). The tropism of the large majority of CRESS DNA viruses is therefore still unknown (66).…”

“…These 21 Rep sequences plus another 5 complete Rep ORFs from contigs (see Table S2 in the supplemental material) were selected for phylogenetic analysis. Ten Rep sequences clustered with a diverse group of genomes recently identified in mammalian fecal samples and labeled smacoviruses (35), but other taxa were widely dispersed throughout the tree (Fig. 6).…”

The fecal virome of South and Central American children with diarrhea includes small circular DNA viral genomes of unknown origin

“…For cycloviruses, the cellular hosts remain unknown but may include mammals and/or insects cells, or conceivably, originate from consumed animals or plants. Another distinct clade of viruses with CRESS-DNA genomes was also described in the feces of chimpanzees and other mammals, including pigs, rats [1, 3–5, 10, 18, 21, 22, 25, 26, 30], and recently humans [14], whose cellular hosts are also unknown. Yet another clade of CRESS-DNA genomes whose cellular hosts are not known was reported in the feces of pigs, seals, dromedaries and humans [4, 24, 27, 30].…”