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Role of the host restriction factor APOBEC3 on papillomavirus evolution
Cody J Warren1, Koenraad Van Doorslaer2, Ahwan Pandey3
1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, USA.
Virus Evolution
|August 30, 2016
Summary
Papillomaviruses (PVs) show depleted TC dinucleotides, suggesting evolution to evade host APOBEC3 restriction. This viral adaptation is more pronounced in mucosal-infecting Alphapapillomaviruses.
Area of Science:
- Virology
- Evolutionary Biology
- Genomics
Background:
- Over 270 papillomavirus (PV) types exist across species, yet drivers of host tropism and oncogenesis remain unclear.
- Host antiviral factors, like cytidine deaminase APOBEC3 enzymes, restrict PV infectivity by editing viral genomes.
- PVs have evolved strategies to counteract host defenses, including APOBEC3-mediated restriction.
Purpose of the Study:
- To investigate if APOBEC3 restriction acted as a selective pressure driving papillomavirus evolution.
- To analyze dinucleotide frequencies in PV genomes to identify patterns related to host defense evasion.
Main Methods:
- Analyzed dinucleotide frequencies in 274 PV genomes from the Papillomavirus Episteme database (PaVE).
- Compared APOBEC3 expression levels in mucosal versus cutaneous skin tissues.
- Used computer modeling to reconstruct ancestral PV genomes and assess TC dinucleotide depletion timing.
Main Results:
- TC dinucleotides, a target for human APOBEC3 proteins, are significantly depleted in PV genomes.
- Mucosal skin exhibits higher basal expression of most APOBEC3 isoforms compared to cutaneous skin.
- Alphapapillomaviruses (alpha-PVs), which infect anogenital mucosa, show the most substantial TC dinucleotide depletion, particularly in protein-coding regions.
Conclusions:
- PVs, especially those in high APOBEC3 environments like mucosa, likely evolved to reduce TC dinucleotides to evade host restriction.
- TC depletion in alpha-PVs occurred after divergence from their common ancestor and is influenced by coding potential.
- This study highlights viral adaptation strategies against host antiviral factors in papillomavirus evolution.
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