CRISPR analysis suggests that small circular single-stranded DNA smacoviruses infect Archaea instead of humans

Smacoviridae is a family of small (~2.5 Kb) CRESS-DNA (Circular Rep Encoding Single-Stranded (ss) DNA) viruses. These viruses have been found in faeces, were thought to infect eukaryotes and are suspected to cause gastrointestinal disease in humans. CRISPR-Cas systems are adaptive immune systems in prokaryotes, wherein snippets of genomes from invaders are stored as spacers that are interspersed between a repeated CRISPR sequence. Here we report several spacer sequences in the faecal archaeon Candidatus Methanomassiliicoccus intestinalis matching smacoviruses, implicating the archaeon as a firm candidate for a host. This finding may be relevant to understanding the potential origin of smacovirus-associated human diseases. Our results support that CRESS-DNA viruses can infect non-eukaryotes, which would mean that smacoviruses are the viruses with the smallest genomes to infect prokaryotes known to date. A probable target strand bias suggests that, in addition to double-stranded DNA, the CRISPR-Cas system can target ssDNA.