Epigenetic Regulation of the Human Papillomavirus Life Cycle

Mac, Michelle; Moody, Cary A.

doi:10.3390/pathogens9060483

Cited by 51 publications

(59 citation statements)

References 150 publications

(209 reference statements)

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“…It is becoming clear that epigenetic modifications are an important factor for the development of HPV-associated cancers (reviewed in Refs. [ [133] , [134] , [135] ]) and during the life cycle of the virus [ 136 ]. Like other tumour virus oncoproteins E1A and SV40 LT [ [137] , [138] , [139] ], E6 and E7 regulate the activity of histone acetyltransferases (HATs), p300 and CBP [ 46 , 47 , 140 , 141 ], reducing E2F- and p53-driven transcription and lowering pRb levels.…”

Section: Epigenetic Regulation and Micrornasmentioning

confidence: 99%

Human papillomavirus E6 and E7: What remains?

Vats

Trejo-Cerro

Thomas

et al. 2021

Tumour Virus Research

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Decades of research on the human papillomavirus oncogenes, E6 and E7, have given us huge amounts of data on their expression, functions and structures. We know much about the very many cellular proteins and pathways that they influence in one way or another. However, much of this information is quite discrete, referring to one activity examined under one condition. It is now time to join the dots to try to understand a larger picture: how, where and when do all these interactions occur... and why? Examining these questions will also show how many of the yet obscure cellular processes work together for cellular and tissue homeostasis in health and disease.

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Section: Epigenetic Regulation and Micrornasmentioning

confidence: 99%

Human papillomavirus E6 and E7: What remains?

Vats

Trejo-Cerro

Thomas

et al. 2021

Tumour Virus Research

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“…Overall, this system allows for the discovery and characterization of host factors that regulate the replication and repair of wild-type and damaged DNA templates. Finally, there is a host of epigenetic alterations that occur on HPV DNA during viral replication, therefore studying the consequences of the disruption of epigenetic regulators is another facet of this assay that could be exploited [ 84 ].…”

Section: Discussionmentioning

confidence: 99%

Using a Human Papillomavirus Model to Study DNA Replication and Repair of Wild Type and Damaged DNA Templates in Mammalian Cells

Das

Bristol

Pichierri

et al. 2020

IJMS

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Human papillomaviruses have 8kbp DNA episomal genomes that replicate autonomously from host DNA. During initial infection, the virus increases its copy number to 20–50 copies per cell, causing torsional stress on the replicating DNA. This activates the DNA damage response (DDR) and HPV replicates its genome, at least in part, using homologous recombination. An active DDR is on throughout the HPV life cycle. Two viral proteins are required for replication of the viral genome; E2 binds to 12bp palindromic sequences around the A/T rich origin of replication and recruits the viral helicase E1 via a protein–protein interaction. E1 forms a di-hexameric complex that replicates the viral genome in association with host factors. Transient replication assays following transfection with E1–E2 expression plasmids, along with an origin containing plasmid, allow monitoring of E1-E2 replication activity. Incorporating a bacterial lacZ gene into the origin plasmid allows for the determination of replication fidelity. Here we describe how we exploited this system to investigate replication and repair in mammalian cells, including using damaged DNA templates. We propose that this system has the potential to enhance the understanding of cellular components involved in DNA replication and repair.

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“…Papillomaviruses also promote various aspects of their life cycle by modulating host epigenetic mechanisms (33), which induces numerous epigenetic changes in host chromatin. Viral proteins bind to and manipulate several host epigenetic modulating enzymes.…”

Section: Viral Epigenome In Papillomavirus Virionsmentioning

confidence: 99%

Histone Modifications in Papillomavirus Virion Minichromosomes

Porter

Liddle

Browne

et al. 2021

mBio

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An unusual feature of papillomaviruses is that their genomes are packaged into virions along with host histones. Viral minichromosomes were visualized as “beads on a string” by electron microscopy in the 1970s but, to date, little is known about the posttranslational modifications of these histones. To investigate this, we analyzed the histone modifications in HPV16/18 quasivirions, wart-derived bovine papillomavirus (BPV1), and wart-derived human papillomavirus type 1 (HPV1) using quantitative mass spectrometry. The chromatin from all three virion samples had abundant posttranslational modifications (acetylation, methylation, and phosphorylation). These histone modifications were verified by acid urea polyacrylamide electrophoresis and immunoblot analysis. Compared to matched host cell controls, the virion minichromosome was enriched in histone modifications associated with active chromatin and depleted for those commonly found in repressed chromatin. We propose that the viral minichromosome acquires specific histone modifications late in infection that are coupled to the mechanisms of viral replication, late gene expression, and encapsidation. We predict that, in turn, these same modifications benefit early stages of infection by helping to evade detection, promoting localization of the viral chromosome to beneficial regions of the nucleus, and promoting early transcription and replication. IMPORTANCE A relatively unique feature of papillomaviruses is that the viral genome is associated with host histones inside the virion. However, little is known about the nature of the epigenome within papillomavirions or its biological relevance to the infectious viral cycle. Here, we define the epigenetic signature of the H3 and H4 histones from HPV16 virions generated in cell culture and native human papillomavirus type 1 (HPV1) and bovine papillomavirus 1 (BPV1) virions isolated from bovine and human wart tissue. We show that native virions are enriched in posttranslational modifications associated with active chromatin and depleted with those associated with repressed chromatin compared to cellular chromatin. Native virions were also enriched in the histone variant H3.3 compared to the canonical histone H3.1. We propose that the composition of virion-packaged chromatin reflects the late stages of the viral life cycle and promotes the early stages of infection by being primed for viral transcription.

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Epigenetic Regulation of the Human Papillomavirus Life Cycle

Cited by 51 publications

References 150 publications

Human papillomavirus E6 and E7: What remains?

Human papillomavirus E6 and E7: What remains?

Using a Human Papillomavirus Model to Study DNA Replication and Repair of Wild Type and Damaged DNA Templates in Mammalian Cells

Histone Modifications in Papillomavirus Virion Minichromosomes

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