Epithelium expressing the E7 oncoprotein of HPV16 attracts immune-modulatory dendritic cells to the skin and suppresses their antigen-processing capacity

Chandra, Janin, Miao, Yan, Romoff, Natasha and Frazer, Ian H. (2016) Epithelium expressing the E7 oncoprotein of HPV16 attracts immune-modulatory dendritic cells to the skin and suppresses their antigen-processing capacity. Plos One, 11 3: . doi:10.1371/journal.pone.0152886


Author Chandra, Janin
Miao, Yan
Romoff, Natasha
Frazer, Ian H.
Title Epithelium expressing the E7 oncoprotein of HPV16 attracts immune-modulatory dendritic cells to the skin and suppresses their antigen-processing capacity
Journal name Plos One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2016-03-31
Year available 2016
Sub-type Article (original research)
DOI 10.1371/journal.pone.0152886
Open Access Status DOI
Volume 11
Issue 3
Total pages 18
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2017
Language eng
Abstract Antigen presenting cells (APCs) in skin can promote either antigen-specific effector functions or antigen tolerance, and thus determine clearance or persistence of cutaneous viral infections. Human papillomavirus (HPV) infections can persist in squamous epithelium in immunocompetent individuals, and some persisting HPV infections, particularly with HPV16, promote malignant epithelial transformation. Here, we investigate whether local expression of the HPV16 protein most associated with malignant transformation, HPV16-E7, affects the phenotype and function of APC subsets in the skin. We demonstrate an expanded population of Langerhans cells in HPV16-E7 transgenic skin with distinct cell surface markers which express immune-modulatory enzymes and cytokines not expressed by cells from non transgenic skin. Furthermore, HPV16-E7 transgene expression in keratinocytes attracts new APC subsets to the epidermis. In vivo migration and transport of antigen to the draining lymph node by these APCs is markedly enhanced in HPV16-E7 expressing skin, whereas antigen-processing, as measured by proteolytic cleavage of DQ-OVA and activation of T cells in vivo by APCs, is significantly impaired. These data suggest that local expression of HPV16-E7 in keratinocytes can contribute to persisting infection with this oncogenic virus, by altering the phenotype and function of local APCs.
Keyword HPV16
Human papillomavirus (HPV)
Antigen presenting cells (APCs)
HPV16-E7
Immune-modulatory
Epidermis
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
UQ Diamantina Institute Publications
 
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