Analysis of the APOBEC3 footprint across the Anelloviridae family.

APOBEC3 proteins are cytidine deaminases that induce cytosine to thymine changes in the DNA strands they recognize as substrates. Editing mediated by these cellular factors modifies sequences in specific nucleotide contexts, leaving a pattern called APOBEC3 footprint. Viruses of the Anelloviridae family possess single-stranded DNA genomes susceptible to these enzymes. This study examined evidence of APOBEC3 activity in a sample of anelloviruses representative of both the nucleotide diversity and the broad host range of this viral family. Reference sequences from 173 anellovirus species classified into 34 genera, associated with different mammals and birds, were analyzed. Higher levels of editing were found in anelloviruses from Primates, both in the negative (genomic) DNA strand and in the positive DNA strand, compared to cases corresponding to Carnivora, Rodentia or birds. Furthermore, a positive correlation was detected between editing signals on both strands, verified exclusively in Primates. In this same group, a negative correlation was observed between viral genome size and APOBEC3 footprint intensity. When analyzing anelloviruses by genus, those present in hominids, such as Betatorquevirus, Gammatorquevirus, and Hetorquevirus, stood out for their high levels of editing. A notable exception was Alphatorquevirus, which showed lower levels, comparable to those of phylogenetically more distant genera associated with non-primate hosts. In turn, a marked contrast was detected between the editing patterns of some Gyrovirus species obtained from humans and those from birds. Taken together, the results suggest a differential impact of APOBEC3 proteins in anelloviruses, which depends on the host type and viral genome size.