The human gut microbiome has been extensively explored, while the archaeal viruses remain largely unknown. Here, we present a comprehensive analysis of the archaeal viruses from the human gut metagenomes and the existing virus collections using the CRISPR spacer and viral signature-based approach. This results in 1279 viral species, of which, 95.2% infect Methanobrevibacteria_A
,
56.5% shared high identity (>95%) with the archaeal proviruses, 37.2% have a host range across archaeal species, and 55.7% are highly prevalent in the human population (>1%). A methanogenic archaeal virus-specific gene for pseudomurein endoisopeptidase (PeiW) frequently occurs in the viral sequences (
n
 = 150). Analysis of 33
Caudoviricetes
viruses with a complete genome often discovers the genes (
integrase
,
n
 = 29;
mazE
,
n
 = 10) regulating the viral lysogenic-lytic cycle, implying the dominance of temperate viruses in the archaeal virome. Together, our work uncovers the unexplored diversity of archaeal viruses, revealing the novel facet of the human gut microbiome.
Human gut archaeal viruses remain largely unknown. Here the authors present a bioinformatic pipeline to identify viruses of human gut archaea, revealing diversity of archaeal viruses, their hosts and their functional gene repertoire in the human gut.