Characterization of the Human Papillomavirus 16 E8 Promoter

  title={Characterization of the Human Papillomavirus 16 E8 Promoter},
  author={Elke Straub and Jasmin Fertey and Marcel Dreer and Thomas Iftner and Frank Stubenrauch},
  journal={Journal of Virology},
  pages={7304 - 7313}
ABSTRACT Persistent infections with certain human papillomaviruses (HPV) such as HPV16 are a necessary risk factor for the development of anogenital and oropharyngeal cancers. HPV16 genomes replicate as low-copy-number plasmids in the nucleus of undifferentiated keratinocytes, which requires the viral E1 and E2 replication proteins. The HPV16 E8^E2C (or E8^E2) protein limits genome replication by repressing both viral transcription and the E1/E2-dependent DNA replication. How E8^E2C expression… 
Interaction of NCOR/SMRT Repressor Complexes with Papillomavirus E8^E2C Proteins Inhibits Viral Replication
The data suggest that the repressive function of E8^E2C is highly conserved among HPV and that it is mediated by an E8-dependent interaction with NCoR/SMRT complexes.
Functions of Papillomavirus E8^E2 Proteins in Tissue Culture and In Vivo
Tissue culture experiments have revealed that E8^E2 modulates long-term maintenance of extrachromosomal genomes, productive replication, and immortalization properties in a virus type-dependent manner, and in vivo experiments have indicated that Mus musculus PV1 E8+E2 is required for tumor formation in immune-deficient mice.
Stochastic Modeling of the Co-Regulation between Early and E8 Promoters in Human Papillomavirus
  • A. Giaretta
  • Biology
    2018 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC)
  • 2018
The model shows how the E8 co-regulation is capable to reject the stochastic noise of E2 gene expression to a higher extent than the early promoter negative auto-feedback, which proves the capability of the E 8 promoter to finely control the HPV genomes copy number.
Identification and Functional Characterization of Phosphorylation Sites of the Human Papillomavirus 31 E8^E2 Protein
The data suggest that phosphorylation of S78 in E8^E2 regulates its repression activity by a novel mechanism, and this seems to be important for the modulation of host cell gene expression but not viral replication.
Contribution of HDAC3 to transcriptional repression by the human papillomavirus 31 E8^E2 protein.
Evidence is provided that transcriptional repression by HPV31 E8^E2 is NCoR/SMRT-dependent but surprisingly always HDAC3-independent when analysing different HPV promoters.
Restriction of viral gene expression and replication prevents immortalization of human keratinocytes by a beta-human papillomavirus
It is shown that immortalization of keratinocytes by the beta-HPV49 genome requires the inactivation of the viral E8^E2 repressor protein and the presence of the E6 and E7 oncoproteins but also of theE1 and E2 replication proteins.
HPV16 and HPV18 Genome Structure, Expression, and Post-Transcriptional Regulation
The genome structures and the updated transcription maps of HPV16 and HPV18 are discussed, and the latest research advances in understanding RNA cis-elements, intron branch point sequences, and RNA-binding proteins in the regulation of viral RNA processing are discussed.
Cottontail Rabbit Papillomavirus E1 and E2 Proteins Mutually Influence Their Subcellular Localizations
The studies have uncovered that E1 and E2 control each other's subcellular localization: direct binding of E2 to E1 can direct E1 to the nucleus independently from the E1 NLS, and E1Can direct E2to the nucleus without an intact NLS or direct binding to E2.
Keratinocyte Differentiation-Dependent Human Papillomavirus Gene Regulation
Current knowledge of how HPV late gene expression is regulated is discussed, which includes how viral genome amplification, virion formation, and release into the environment from the surface of the epithelium are regulated.


Repression of HPV 16 early region transcription by the E 2 protein
It is demonstrated that the E2 protein is primarily a transcriptional repressor when expressed from the virus, and this data provides important insight into which E1 and E2 functions are optimal targets for anti-viral therapies.
The Viral E8^E2C Repressor Limits Productive Replication of Human Papillomavirus 16
The data indicate that the E8^E2C repressor limits viral transcription and replication throughout the complete life cycle of HPV16.
Genetic Analysis of the Human Papillomavirus Type 31 Differentiation-Dependent Late Promoter
Mapped viral DNA elements that control transcriptional activity from p742 and mapped elements in the region of p741 that confer responsiveness to differentiation and show that the upstream regulatory region does not contribute to the differentiation response of p 742.
The human papillomavirus type 18 (HPV18) replication protein E1 is a transcriptional activator when interacting with HPV18 E2.
It is shown that the HPV18 E1 protein can activate transcription when targeted to the DNA by fusion of the complete polypeptide with the BPV1 E2 C-terminus dimerization/DNA binding domain, implying that HPV 18 E1 is an intrinsic transcriptional activator, though less potent than E2.
The E8 Domain Confers a Novel Long-Distance Transcriptional Repression Activity on the E8^E2C Protein of High-Risk Human Papillomavirus Type 31
A novel long-distance repression activity of the E8 domain enabled E8^E2C to inhibit the HPV6a P2 promoter and minimal-promoter constructs containing E2 binding sites and might contribute to the progression of high-risk HPV-induced lesions.
The E8∧E2 Gene Product of Human Papillomavirus Type 16 Represses Early Transcription and Replication but Is Dispensable for Viral Plasmid Persistence in Keratinocytes
Primary human keratinocytes immortalized by the HPV-16 E8 mutant genome contain more than eightfold-higher levels of unintegrated plasmid than the wt, demonstrating that 16-E8∧E2 limits the viral copy number but is not required for plasmids persistence and maintenance.
The E8^E2C Protein, a Negative Regulator of Viral Transcription and Replication, Is Required for Extrachromosomal Maintenance of Human Papillomavirus Type 31 in Keratinocytes
High-level expression of E8 ̂E2C from heterologous vectors was found to inhibit E1-E2-dependent DNA replication of an HPV31 origin of replication construct as well as to interfere with E2's ability to transactivate reporter gene constructs, and HPV31 E 8 ⩽C strongly repressed the basal activity of the major viral early promoter P97 independent of E2.
NCoR1 Mediates Papillomavirus E8^E2C Transcriptional Repression
An unbiased proteomic analysis was performed from which six high-confidence candidate interacting proteins (HCIPs) for E8^E2C were identified; the top two are NCoR1 and TBLR1; and small interfering RNA (siRNA) knockdown studies demonstrated the involvement of N coR1/HDAC3 in the E8-dependent repression of the viral long control region (LCR) promoter.