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Epstein–Barr Virus Infection of Pseudostratified Nasopharyngeal Epithelium Disrupts Epithelial Integrity
SIMPLE SUMMARY: Nasopharyngeal carcinoma is associated with Epstein-Barr virus (EBV) infection and originates junction of the oropharynx and nasal cavity, where stratified squamous epithelium and respiratory epithelium are the lining. To elucidate the mechanisms by which EBV transforms the nasophary...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564236/ https://www.ncbi.nlm.nih.gov/pubmed/32972034 http://dx.doi.org/10.3390/cancers12092722 |
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author | Yu, Fenggang Lu, Yanan Li, Yingying Uchio, Yuji Pangnguriseng, Utomo Andi Kartika, Andy Visi Iizasa, Hisashi Yoshiyama, Hironori Loh, Kwok Seng |
author_facet | Yu, Fenggang Lu, Yanan Li, Yingying Uchio, Yuji Pangnguriseng, Utomo Andi Kartika, Andy Visi Iizasa, Hisashi Yoshiyama, Hironori Loh, Kwok Seng |
author_sort | Yu, Fenggang |
collection | PubMed |
description | SIMPLE SUMMARY: Nasopharyngeal carcinoma is associated with Epstein-Barr virus (EBV) infection and originates junction of the oropharynx and nasal cavity, where stratified squamous epithelium and respiratory epithelium are the lining. To elucidate the mechanisms by which EBV transforms the nasopharyngeal epithelium, a pseudostratified multiple-layer model with cilia forming on the apical surface by air-liquid interface (ALI) culture of primary nasopharyngeal epithelial cells was established. We showed: (1) ALI cultures formed stratified epithelia and maintained the diversity of cells found in the airway epithelium, such as ciliated, muco-secretory, and basal cells. (2) Polarized stratified epithelium was more susceptible to EBV infection than monolayer cells. (3) EBV infection in ALI cultures was verified by showing EBV-encoded RNA expressions. (4) EBV infection disrupted the integrity of the epithelium. Thus, our model can be used not only to examine the pathogenesis of pre-neoplastic EBV-infected cells, but also to develop anti-EBV therapy or early stage NPC treatment. ABSTRACT: Epstein–Barr virus (EBV) is a human oncogenic virus that causes several types of tumor, such as Burkitt’s lymphoma and nasopharyngeal carcinoma (NPC). NPC tumor cells are clonal expansions of latently EBV-infected epithelial cells. However, the mechanisms by which EBV transforms the nasopharyngeal epithelium is hampered, because of the lack of good in vitro model to pursue oncogenic process. Our primary nasopharyngeal epithelial cell cultures developed pseudostratified epithelium at the air-liquid interface, which was susceptible to EBV infection. Using the highly sensitive RNA in situ hybridization technique, we detected viral infection in diverse cell types, including ciliated cells, goblet cells, and basal cells. EBV-encoded small RNA-positive cells were more frequently detected in the suprabasal layer than in the basal layer. We established the most physiologically relevant EBV infection model of nasopharyngeal epithelial cells. This model will advance our understanding of EBV pathogenesis in the development of NPC. |
format | Online Article Text |
id | pubmed-7564236 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75642362020-10-26 Epstein–Barr Virus Infection of Pseudostratified Nasopharyngeal Epithelium Disrupts Epithelial Integrity Yu, Fenggang Lu, Yanan Li, Yingying Uchio, Yuji Pangnguriseng, Utomo Andi Kartika, Andy Visi Iizasa, Hisashi Yoshiyama, Hironori Loh, Kwok Seng Cancers (Basel) Article SIMPLE SUMMARY: Nasopharyngeal carcinoma is associated with Epstein-Barr virus (EBV) infection and originates junction of the oropharynx and nasal cavity, where stratified squamous epithelium and respiratory epithelium are the lining. To elucidate the mechanisms by which EBV transforms the nasopharyngeal epithelium, a pseudostratified multiple-layer model with cilia forming on the apical surface by air-liquid interface (ALI) culture of primary nasopharyngeal epithelial cells was established. We showed: (1) ALI cultures formed stratified epithelia and maintained the diversity of cells found in the airway epithelium, such as ciliated, muco-secretory, and basal cells. (2) Polarized stratified epithelium was more susceptible to EBV infection than monolayer cells. (3) EBV infection in ALI cultures was verified by showing EBV-encoded RNA expressions. (4) EBV infection disrupted the integrity of the epithelium. Thus, our model can be used not only to examine the pathogenesis of pre-neoplastic EBV-infected cells, but also to develop anti-EBV therapy or early stage NPC treatment. ABSTRACT: Epstein–Barr virus (EBV) is a human oncogenic virus that causes several types of tumor, such as Burkitt’s lymphoma and nasopharyngeal carcinoma (NPC). NPC tumor cells are clonal expansions of latently EBV-infected epithelial cells. However, the mechanisms by which EBV transforms the nasopharyngeal epithelium is hampered, because of the lack of good in vitro model to pursue oncogenic process. Our primary nasopharyngeal epithelial cell cultures developed pseudostratified epithelium at the air-liquid interface, which was susceptible to EBV infection. Using the highly sensitive RNA in situ hybridization technique, we detected viral infection in diverse cell types, including ciliated cells, goblet cells, and basal cells. EBV-encoded small RNA-positive cells were more frequently detected in the suprabasal layer than in the basal layer. We established the most physiologically relevant EBV infection model of nasopharyngeal epithelial cells. This model will advance our understanding of EBV pathogenesis in the development of NPC. MDPI 2020-09-22 /pmc/articles/PMC7564236/ /pubmed/32972034 http://dx.doi.org/10.3390/cancers12092722 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yu, Fenggang Lu, Yanan Li, Yingying Uchio, Yuji Pangnguriseng, Utomo Andi Kartika, Andy Visi Iizasa, Hisashi Yoshiyama, Hironori Loh, Kwok Seng Epstein–Barr Virus Infection of Pseudostratified Nasopharyngeal Epithelium Disrupts Epithelial Integrity |
title | Epstein–Barr Virus Infection of Pseudostratified Nasopharyngeal Epithelium Disrupts Epithelial Integrity |
title_full | Epstein–Barr Virus Infection of Pseudostratified Nasopharyngeal Epithelium Disrupts Epithelial Integrity |
title_fullStr | Epstein–Barr Virus Infection of Pseudostratified Nasopharyngeal Epithelium Disrupts Epithelial Integrity |
title_full_unstemmed | Epstein–Barr Virus Infection of Pseudostratified Nasopharyngeal Epithelium Disrupts Epithelial Integrity |
title_short | Epstein–Barr Virus Infection of Pseudostratified Nasopharyngeal Epithelium Disrupts Epithelial Integrity |
title_sort | epstein–barr virus infection of pseudostratified nasopharyngeal epithelium disrupts epithelial integrity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564236/ https://www.ncbi.nlm.nih.gov/pubmed/32972034 http://dx.doi.org/10.3390/cancers12092722 |
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