Related Experiment Video

Updated: May 26, 2026

Use of Interferon-γ Enzyme-linked Immunospot Assay to Characterize Novel T-cell Epitopes of Human Papillomavirus
13:41

Use of Interferon-γ Enzyme-linked Immunospot Assay to Characterize Novel T-cell Epitopes of Human Papillomavirus

Published on: March 8, 2012

Human papillomavirus 8 E6 disrupts terminal skin differentiation and prevents pro-Caspase-14 cleavage

Siamaque Kazem1, Els van der Meijden, Linda Struijk

  • 1Department of Medical Microbiology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.

Virus Research
|January 11, 2012
PubMed

Insights

Human papillomavirus type 8 E6 protein disrupts keratinocyte differentiation, preventing stratum corneum formation and leading to accumulation of specific proteins. This suggests HPV8 E6 inhibits key differentiation pathways in skin cells.

Area of Science:

  • Dermatology
  • Virology
  • Cell Biology

Background:

  • Betapapillomavirus (betaPV) E6/E7 genes are known to disrupt keratinocyte differentiation and apoptosis.
  • Late-terminal keratinocyte differentiation shares characteristics with apoptosis, including DNA fragmentation and caspase activation.

Purpose of the Study:

  • To investigate the disruption of keratinocyte differentiation by human papillomavirus (HPV)8 in organotypic skin raft cultures.
  • To determine the specific role of HPV8 E6 and E7 genes in this process.

Main Methods:

  • Organotypic skin (raft) cultures of primary (PHK) and immortalized (N/TERT) human keratinocytes.
  • Immunohistochemical and immunofluorescence analyses of HPV5 and HPV8 E6/E7-expressing keratinocytes.
  • Western blot analysis of raft lysates.

Main Results:

  • HPV8 E6/E7 expression in PHK rafts led to thickened rafts and absent stratum corneum formation.
  • The aberrant morphology was specifically linked to E6 expression, not E7.
  • HPV8 E6 rafts showed increased Filaggrin and pro-Caspase-14 positive cells, but lacked detectable Caspase-14 subunits.

Conclusions:

  • HPV8 E6 prevents late-terminal keratinocyte differentiation in raft cultures, causing stratification absence.
  • This differentiation arrest is associated with Filaggrin and pro-Caspase-14 accumulation and failure of Caspase-14 subunit expression.
  • This suggests abrogation of Caspase-14 activation and Filaggrin maturation in HPV8 E6-expressing keratinocytes.

More Related Videos

Generation of Organotypic Raft Cultures from Primary Human Keratinocytes07:26

Generation of Organotypic Raft Cultures from Primary Human Keratinocytes

Published on: February 22, 2012

Using Next Generation Sequencing to Identify Mutations Associated with Repair of a CAS9-induced Double Strand Break Near the CD4 Promoter06:59

Using Next Generation Sequencing to Identify Mutations Associated with Repair of a CAS9-induced Double Strand Break Near the CD4 Promoter

Published on: March 31, 2022

Related Concept Videos

Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart, a...
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...