Coevolutionary Analysis Implicates Toll-Like Receptor 9 in Papillomavirus Restriction.

Area of Science:

• Virology
• Immunology
• Evolutionary Biology

Background:

• DNA viruses trigger innate immune responses via pattern recognition receptors (PRRs), necessitating viral evasion strategies.
• Papillomaviruses utilize a unique trafficking pathway, potentially avoiding cytoplasmic PRRs but risking detection by Toll-like receptor 9 (TLR9) during capsid uncoating.

Purpose of the Study:

• To investigate how papillomaviruses evade innate immune detection, specifically by TLR9.
• To characterize novel bat papillomaviruses and their genomic adaptations.
• To explore the coevolutionary dynamics between papillomaviruses and bats.

Main Methods:

• Genomic analysis of new bat papillomaviruses.
• Molecular archeology to reconstruct viral evolutionary history.
• Comparative analysis of viral genome nucleotide composition.
• Examination of human papillomaviruses and TLR9 recognition sites.

Main Results:

• Two new bat papillomaviruses possess genomes with altered nucleotide compositions, specifically reduced CpG dinucleotides, to avoid TLR9 detection.
• Evidence suggests TLR9 functions as a PRR during papillomavirus infection.
• TLR9 is under evolutionary selection in bats, indicating host-pathogen coevolution.
• Cancer-associated human papillomaviruses also show reduced CpG motifs in TLR9 recognition complexes.

Conclusions:

• Papillomaviruses have evolved mechanisms, including genomic alterations, to evade innate immune sensing by TLR9.
• This study provides the first direct evidence of coevolution between papillomaviruses and bats.
• Genomic adaptations to avoid TLR9 may be a conserved strategy among papillomaviruses.