Anelloviruses, common in humans and mammals, deemed part of healthy virome

Anelloviruses, which are found in various mammals including humans, possess compact circular DNA genomes and have no known disease associations. A recent study published in Virus Evolution by Dr. Rafaela S. Fontenele and her team reveals an evolutionary link with circoviruses, suggesting adaptation to host immune pressure. The research also proposes the recognition of a new phylum "Commensaviricota" within the realm Monodnaviria.

For a long time, Anelloviruses have been viewed as part of the 'healthy virome', without any identified links to diseases. Characterized by small circular single-stranded DNA genomes, these viruses encode proteins that are distinct from those of other known viruses. Despite their prevalence, anelloviruses have been excluded from the Monodnaviria realm, making them the only family of eukaryotic ssDNA viruses not classified within this framework. To decipher the enigma surrounding these viruses, researchers sequenced over 250 anellovirus genomes from diverse sources, including Weddell seals in Antarctica and a grizzly bear in the United States.

Through advanced sequencing and structural modeling using AlphaFold2, Fontenele's study revealed that anellovirus protein ORF1, shared by all Anelloviridae genera, adopts a jelly-roll fold typical of viral capsid proteins. This discovery establishes an evolutionary connection to other eukaryotic ssDNA viruses, particularly circoviruses. Notably different from other ssDNA viruses is that ORF1 in anelloviruses displays significant size variation due to insertions into the jelly-roll domain. A key finding is an insertion forming a projection domain predicted to influence virus-host interactions. The outermost region of this domain has been identified as a mutational hotspot indicating rapid evolution prompted by host immune responses.

In light of these insights, the researchers propose assigning Anelloviridae to a new phylum named 'Commensaviricota' and including it in the kingdom Shotokuvirae within the Monodnaviria realm, alongside Cressdnaviricota and Cossaviricota. These findings broaden our understanding of anellovirus diversity and shed light on the divergence of anellovirus ORF1 proteins from conventional jelly-roll capsid proteins.

Oxford Academic: Anamarija Butkovic, et al. Evolution of anelloviruses from a circovirus-like ancestor through gradual augmentation of the jelly-roll capsid protein, Virus Evolution (May 2023). DOI: https://doi.org/10.1093/ve/vead035