The crAss-like Phage Group: How Metagenomics Reshaped the Human Virome

Metagenomics is currently the primary means for identifying new viruses. One of the most impactful metagenomic discoveries is that of crAssphage, the most abundant human-associated virus that is found in about 50% of human gut viromes where it can comprise up to 90% of the virus sequences. Although initial genome analysis of crAssphage failed to detect related phages, or functionally annotate most of the genes, subsequent reanalysis with powerful computational methods and larger databases led to the identification of an expansive group of crAss-like phages. The functions of most crAssphage proteins were predicted, including unusual ones such as giant RNA polymerase polyproteins. The host range of the crAss-like phages consists of various members of the bacterial phylum Bacteroidetes as demonstrated by CRISPR spacer analysis and by analysis of genes acquired by phages from the hosts. New metagenomic studies vastly expanded the crAss-like phage group and demonstrated its global spread and ancient association with primates. The first members of the crAss-like group was recently isolated and shown to infect the bacterium Bacteroides intestinales. Characterization of this phage validated the predicted podovirus-like virion structure and the identity of the major capsid protein and other predicted virion proteins, including three RNA polymerase subunits.