Footprint of the host restriction factors APOBEC3 on the genome of human viruses

APOBEC3 enzymes are innate immune effectors that introduce mutations into viral genomes. These enzymes are cytidine deaminases which transform cytosine into uracil. They preferentially mutate cytidine preceded by thymidine making the 5’TC motif their favored target. Viruses have evolved different strategies to evade APOBEC3 restriction. Certain viruses actively encode viral proteins antagonizing the APOBEC3s, others passively face the APOBEC3 selection pressure thanks to a depleted genome for APOBEC3-targeted motifs. Hence, the APOBEC3s left on the genome of certain viruses an evolutionary footprint.

The aim of our study is the identification of these viruses having a genome shaped by the APOBEC3s. We analyzed the genome of 33,400 human viruses for the depletion of APOBEC3-favored motifs. We demonstrate that the APOBEC3 selection pressure impacts at least 22% of all currently annotated human viral species. The papillomaviridae and polyomaviridae are the most intensively footprinted f..., The A3 evolutionary footprint left on viral genomes is defined as the under-representation of A3-targeted motifs. Because most of the A3 proteins favors deamination of cytosine to uracil in a 5’TC dinucleotide context, we have chosen to look for the under-representation of the 5’TC motif. We differentiate three K-mers containing the TC motif; one K-mer having the C in the first position of the codon (NNTCNN), one K-mer having the C in the second position of the codon (TCN) and one K-mer having the C in the third position of the codon (NTC). A3-introduced deamination of cytosine in viral genome produces an uracil that can be fixed in the form of thymidine after genome replication. This transition will have different impacts depending on the position of the mutated C. The C to T mutation will be non-synonymous if the C is at the first or second position of the codon. However, if the mutated C occupies the third position of the codon, the C to T mutation will always be synonymous. Therefor..., S1 Table: Genomic K-mer ratios for human viruses.
Observed/expected K-mer ratios for each genomic human viral sequence.
 
S2 Table: Genic K-mer ratios for human viruses.
Observed/expected K-mer ratios for each genic human viral sequence.
 
S3 Table: Genomic K-mer ratios for non-human viruses.
Observed/expected K-mer ratios for each genomic and genic non-human viral sequence.