Woei Ling Peh

Publications (8)19.56 Total impact

• Article: Characterization of beta papillomavirus E4 expression in tumours from Epidermodysplasia Verruciformis patients and in experimental models.

  Cinzia Borgogna, Elisa Zavattaro, Marco De Andrea, Heather M Griffin, Valentina Dell'Oste, Barbara Azzimonti, Manuela M Landini, Woei Ling Peh, Herbert Pfister, John Doorbar, Santo Landolfo, Marisa Gariglio
  [show abstract] [hide abstract]
  ABSTRACT: This study provides a first characterisation of β-HPV life-cycle events in tumours abscised from EV patients (the human model of β-HPV-induced skin cancer), and shows how changes in E4 expression patterns relate to disease severity. β-HPV life-cycle has also been reconstructed in organotypic raft cultures created using EV-derived keratinocytes. In EV lesions and raft cultures, abundant cytoplasmic E4 expression was detectable in differentiating cells along with viral genome amplification as reported for other HPV types. E4 expression was also seen in PCNA-positive basal cells in some EV skin cancers as well as in tumours from HPV8CER (Complete Early Region) transgenic mice. In these lesions, E4 staining extended throughout the full thickness of the epithelium and was apparent in the markedly atypical cells. The loss of such staining at the tumour border suggests a distinct type of E4 dysregulation that may be exploited as a marker of viral expression during β-HPV-associated skin cancer progression.
  Virology 01/2012; 423(2):195-204. · 3.35 Impact Factor
• Article: Human papillomavirus type 16 E1circumflexE4 contributes to multiple facets of the papillomavirus life cycle.

  Tomomi Nakahara, Woei Ling Peh, John Doorbar, Denis Lee, Paul F Lambert
  [show abstract] [hide abstract]
  ABSTRACT: The life cycle of human papillomaviruses (HPVs) is tightly linked to the differentiation program of the host's stratified epithelia that it infects. E1(circumflex)E4 is a viral protein that has been ascribed multiple biochemical properties of potential biological relevance to the viral life cycle. To identify the role(s) of the viral E1(circumflex)E4 protein in the HPV life cycle, we characterized the properties of HPV type 16 (HPV16) genomes harboring mutations in the E4 gene in NIKS cells, a spontaneously immortalized keratinocyte cell line that when grown in organotypic raft cultures supports the HPV life cycle. We learned that E1(circumflex)E4 contributes to the replication of the viral plasmid genome as a nuclear plasmid in basal cells, in which we also found E1(circumflex)E4 protein to be expressed at low levels. In the suprabasal compartment of organotypic raft cultures harboring E1(circumflex)E4 mutant HPV16 genomes there were alterations in the frequency of suprabasal cells supporting DNA synthesis, the levels of viral DNA amplification, and the degree to which the virus perturbs differentiation. Interestingly, the comparison of the phenotypes of various mutations in E4 indicated that the E1(circumflex)E4 protein-encoding requirements for these various processes differed. These data support the hypothesis that E1(circumflex)E4 is a multifunctional protein and that the different properties of E1(circumflex)E4 contribute to different processes in both the early and late stages of the virus life cycle.
  Journal of Virology 11/2005; 79(20):13150-65. · 5.40 Impact Factor
• Source

  Available from: Jonathan B A Millar

  Article: Human papillomavirus type 16 E1 E4-induced G2 arrest is associated with cytoplasmic retention of active Cdk1/cyclin B1 complexes.

  Clare E Davy, Deborah J Jackson, Kenneth Raj, Woei Ling Peh, Shirley A Southern, Papia Das, Rina Sorathia, Peter Laskey, Kate Middleton, Tomomi Nakahara, Qian Wang, Phillip J Masterson, Paul F Lambert, Scott Cuthill, Jonathan B A Millar, John Doorbar
  [show abstract] [hide abstract]
  ABSTRACT: Human papillomavirus type 16 (HPV16) can cause cervical cancer. Expression of the viral E1 E4 protein is lost during malignant progression, but in premalignant lesions, E1 E4 is abundant in cells supporting viral DNA amplification. Expression of 16E1 E4 in cell culture causes G2 cell cycle arrest. Here we show that unlike many other G2 arrest mechanisms, 16E1 E4 does not inhibit the kinase activity of the Cdk1/cyclin B1 complex. Instead, 16E1 E4 uses a novel mechanism in which it sequesters Cdk1/cyclin B1 onto the cytokeratin network. This prevents the accumulation of active Cdk1/cyclin B1 complexes in the nucleus and hence prevents mitosis. A mutant 16E1 E4 (T22A, T23A) which does not bind cyclin B1 or alter its intracellular location fails to induce G2 arrest. The significance of these results is highlighted by the observation that in lesions induced by HPV16, there is evidence for Cdk1/cyclin B1 activity on the keratins of 16E1 E4-expressing cells. We hypothesize that E1 E4-induced G2 arrest may play a role in creating an environment optimal for viral DNA replication and that loss of E1 E4 expression may contribute to malignant progression.
  Journal of Virology 05/2005; 79(7):3998-4011. · 5.40 Impact Factor
• Article: Detection of papillomavirus proteins and DNA in paraffin-embedded tissue sections.

  Woei Ling Peh, John Doorbar
  [show abstract] [hide abstract]
  ABSTRACT: The key events during the papillomavirus life cycle can be mapped in infected tissue samples by antibody detection and in situ hybridization. The ease of immuno-detection varies for different proteins and is dependent on antigen availability. Epitope exposure is sometimes necessary, because the antigen may become masked after formalin fixation and paraffin embedding of the infected tissue. Visualization of both nucleic acid and protein targets can be done simultaneously by combining in situ hybridization and immuno-detection methods.
  Methods in molecular medicine 02/2005; 119:49-59.
• Article: Human Papillomavirus Type 16 E1 E4Induced G2 Arrest Is Associated with Cytoplasmic Retention of Active Cdk1/Cyclin B1 Complexes

  Clare E. Davy, Deborah J. Jackson, Kenneth Raj, Woei Ling Peh, Papia Das, Rina Sorathia, Peter Laskey, Kate Middleton, Tomomi Nakahara, Qian Wang, Phillip J. Masterson, Paul F. Lambert
  Journal of Virology - J VIROL. 01/2005; 79(7):3998-4011.
• Article: Human Papillomavirus Type 16 E1 E4 Contributes to Multiple Facets of the Papillomavirus Life Cycle

  Tomomi Nakahara, Woei Ling Peh, John Doorbar, Denis Lee, Paul F. Lambert
  [show abstract] [hide abstract]
  ABSTRACT: The life cycle of human papillomaviruses (HPVs) is tightly linked to the differentiation program of the host's stratified epithelia that it infects. E1∧E4 is a viral protein that has been ascribed multiple biochemical properties of potential biological relevance to the viral life cycle. To identify the role(s) of the viral E1∧E4 protein in the HPV life cycle, we characterized the properties of HPV type 16 (HPV16) genomes harboring mutations in the E4 gene in NIKS cells, a spontaneously immortalized keratinocyte cell line that when grown in organotypic raft cultures supports the HPV life cycle. We learned that E1∧E4 contributes to the replication of the viral plasmid genome as a nuclear plasmid in basal cells, in which we also found E1∧E4 protein to be expressed at low levels. In the suprabasal compartment of organotypic raft cultures harboring E1∧E4 mutant HPV16 genomes there were alterations in the frequency of suprabasal cells supporting DNA synthesis, the levels of viral DNA amplification, and the degree to which the virus perturbs differentiation. Interestingly, the comparison of the phenotypes of various mutations in E4 indicated that the E1∧E4 protein-encoding require- ments for these various processes differed. These data support the hypothesis that E1∧E4 is a multifunctional protein and that the different properties of E1∧E4 contribute to different processes in both the early and late
  Journal of Virology - J VIROL. 01/2005; 79(20):13150-13165.
• Article: Life cycle heterogeneity in animal models of human papillomavirus-associated disease.

  Woei Ling Peh, Kate Middleton, Neil Christensen, Philip Nicholls, Kiyofumi Egawa, Karl Sotlar, Janet Brandsma, Alan Percival, Jon Lewis, Wen Jun Liu, John Doorbar
  [show abstract] [hide abstract]
  ABSTRACT: Animal papillomaviruses are widely used as models to study papillomavirus infection in humans despite differences in genome organization and tissue tropism. Here, we have investigated the extent to which animal models of papillomavirus infection resemble human disease by comparing the life cycles of 10 different papillomavirus types. Three phases in the life cycles of all viruses were apparent using antibodies that distinguish between early events, the onset of viral genome amplification, and the expression of capsid proteins. The initiation of these phases follows a highly ordered pattern that appears important for the production of virus particles. The viruses examined included canine oral papillomavirus, rabbit oral papillomavirus (ROPV), cottontail rabbit papillomavirus (CRPV), bovine papillomavirus type 1, and human papillomavirus types 1, 2, 11, and 16. Each papillomavirus type showed a distinctive gene expression pattern that could be explained in part by differences in tissue tropism, transmission route, and persistence. As the timing of life cycle events affects the accessibility of viral antigens to the immune system, the ideal model system should resemble human mucosal infection if vaccine design is to be effective. Of the model systems examined here, only ROPV had a tissue tropism and a life cycle organization that resembled those of the human mucosal types. ROPV appears most appropriate for studies of the life cycles of mucosal papillomavirus types and for the development of prophylactic vaccines. The persistence of abortive infections caused by CRPV offers advantages for the development of therapeutic vaccines.
  Journal of Virology 11/2002; 76(20):10401-16. · 5.40 Impact Factor
• Article: The role of the papillomavirus E4 protein during the late stage of the viral life cycle using in vivo model systems /

  Woei Ling. Peh
  [show abstract] [hide abstract]
  ABSTRACT: Thesis (Ph.D.)--University of London, 2003.