Coevolutionary Analysis Implicates Toll-Like Receptor 9 in Papillomavirus Restriction

King, Kelly M.; Larsen, Brendan B.; Gryseels, Sophie; Richet, Cécile; Kraberger, Simona; Jackson, Robert; Worobey, Michael; Harrison, Joseph S.; Varsani, Arvind; Doorslaer, Koenraad Van

doi:10.1128/mbio.00054-22

Cited by 12 publications

(12 citation statements)

References 150 publications

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“…A recent study has shown direct evidence of virus-host coevolution in a subclade including several bat and other mammalian papillomaviruses (46). Since our MAVGs were embedded in this subclade (global tree not shown), we decided to replicate this previous analysis to test whether the observed cross-species transmission events could compromise coevolution detection.…”

Section: Resultsmentioning

confidence: 99%

Full genome sequencing of dozens of new DNA viruses found in Spanish bat faeces

Buigues,

Vinals,

Martinez-Recio

et al. 2024

Preprint

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Bats are natural hosts of multiple viruses, many of which have clear zoonotic potential. The search for emerging viruses has been aided by the implementation of metagenomic tools, which have also enabled the detection of unprecedented viral diversity. Currently, this search is mainly focused on RNA viruses, which are largely over-represented in databases. To compensate for this research bias, we analyzed fecal samples from 189 Spanish bats belonging to 22 different species using viral metagenomics. This allowed us to identify 50 complete or near-complete viral genomes belonging to the families Adenoviridae, Circoviridae, Genomoviridae, Papillomaviridae, Parvoviridae, Polyomaviridae and Smacoviridae. Of these, 28 could constitute new species, doubling the number of viruses currently described in Europe. These findings open the door to a more thorough analysis of bat DNA viruses and their zoonotic potential.

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Section: Resultsmentioning

confidence: 99%

Full genome sequencing of dozens of new DNA viruses found in Spanish bat faeces

Buigues,

Vinals,

Martinez-Recio

et al. 2024

Preprint

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“…In the genomes of small animal dsDNA viruses, such as polyomaviruses and papillomaviruses, CpG dinucleotides are under-represented [129]. However, these viruses are not known to be restricted by ZAP, and their dinucleotide composition can instead be partly accounted for by methylation avoidance and/or by avoidance of TLR9 recognition [63,130,131]. In herpesviruses, large dsDNA viruses with genomes comparable in size to those of poxviruses, genetic diversity is very large and so is the diversity of genomic composition biases: alphaherpesviruses do not show CpG depletion, whereas many gammaherpesviruses do, and in betaherpesviruses, specific depletion of CpG is observed in immediate early (IE) genes only [69,132].…”

Section: Discussionmentioning

confidence: 99%

Evolution and diversity of nucleotide and dinucleotide composition in poxviruses

Molteni,

Forni,

Cagliani

et al. 2023

Journal of General Virology

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Poxviruses (family Poxviridae) have long dsDNA genomes and infect a wide range of hosts, including insects, birds, reptiles and mammals. These viruses have substantial incidence, prevalence and disease burden in humans and in other animals. Nucleotide and dinucleotide composition, mostly CpG and TpA, have been largely studied in viral genomes because of their evolutionary and functional implications. We analysed here the nucleotide and dinucleotide composition, as well as codon usage bias, of a set of representative poxvirus genomes, with a very diverse host spectrum. After correcting for overall nucleotide composition, entomopoxviruses displayed low overall GC content, no enrichment in TpA and large variation in CpG enrichment, while chordopoxviruses showed large variation in nucleotide composition, no obvious depletion in CpG and a weak trend for TpA depletion in GC-rich genomes. Overall, intergenome variation in dinucleotide composition in poxviruses is largely accounted for by variation in overall genomic GC levels. Nonetheless, using vaccinia virus as a model, we found that genes expressed at the earliest times in infection are more CpG-depleted than genes expressed at later stages. This observation has parallels in betahepesviruses (also large dsDNA viruses) and suggests an antiviral role for the innate immune system (e.g. via the zinc-finger antiviral protein ZAP) in the early phases of poxvirus infection. We also analysed codon usage bias in poxviruses and we observed that it is mostly determined by genomic GC content, and that stratification after host taxonomy does not contribute to explaining codon usage bias diversity. By analysis of within-species diversity, we show that genomic GC content is the result of mutational biases. Poxvirus genomes that encode a DNA ligase are significantly AT-richer than those that do not, suggesting that DNA repair systems shape mutation biases. Our data shed light on the evolution of poxviruses and inform strategies for their genetic manipulation for therapeutic purposes.

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“…The endocytic pathway of HPV entry could expose viral DNA to endosomal TRL9, which recognizes unmethylated CpG motifs in dsDNA viral genomes [79,80]. Interestingly, however, many papillomaviruses exhibit reduced CpG content, including cancer-associated Alphapapillomaviruses, which may prevent detection by TLR9 [81][82][83]. Whether HPV genomes are hypomethylated in the virion is currently unknown.…”

Section: Activation Of the Innate Immune Response Upon Initial Hpv In...mentioning

confidence: 99%

Regulation of the Innate Immune Response during the Human Papillomavirus Life Cycle

Moody

2022

Viruses

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High-risk human papillomaviruses (HR HPVs) are associated with multiple human cancers and comprise 5% of the human cancer burden. Although most infections are transient, persistent infections are a major risk factor for cancer development. The life cycle of HPV is intimately linked to epithelial differentiation. HPVs establish infection at a low copy number in the proliferating basal keratinocytes of the stratified epithelium. In contrast, the productive phase of the viral life cycle is activated upon epithelial differentiation, resulting in viral genome amplification, high levels of late gene expression, and the assembly of virions that are shed from the epithelial surface. Avoiding activation of an innate immune response during the course of infection plays a key role in promoting viral persistence as well as completion of the viral life cycle in differentiating epithelial cells. This review highlights the recent advances in our understanding of how HPVs manipulate the host cell environment, often in a type-specific manner, to suppress activation of an innate immune response to establish conditions supportive of viral replication.

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Coevolutionary Analysis Implicates Toll-Like Receptor 9 in Papillomavirus Restriction

Cited by 12 publications

References 150 publications

Full genome sequencing of dozens of new DNA viruses found in Spanish bat faeces

Full genome sequencing of dozens of new DNA viruses found in Spanish bat faeces

Evolution and diversity of nucleotide and dinucleotide composition in poxviruses

Regulation of the Innate Immune Response during the Human Papillomavirus Life Cycle

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