High Levels of EBV-Encoded RNA 1 (EBER1) Trigger Interferon and Inflammation-Related Genes in Keratinocytes Expressing HPV16 E6/E7
| Autor: | Sinéad M. Lougheed, Tipaya Ekalaksananan, Renske D.M. Steenbergen, D. Michiel Pegtel, Jaap M. Middeldorp, Octavia Ramayanti, Monique A. J. van Eijndhoven, Chamsai Pientong, Sirinart Aromseree |
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| Přispěvatelé: | CCA - Cancer biology and immunology, AII - Infectious diseases, Pathology, Medical oncology |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Keratinocytes B Cells Physiology Papillomavirus E7 Proteins Cell lcsh:Medicine Gene Expression Exosomes Pathology and Laboratory Medicine White Blood Cells 0302 clinical medicine Interferon Animal Cells Immune Physiology hemic and lymphatic diseases Medicine and Health Sciences lcsh:Science Immune Response Innate Immune System Human papillomavirus 16 Multidisciplinary virus diseases Transfection medicine.anatomical_structure Medical Microbiology 030220 oncology & carcinogenesis Viral Pathogens Viruses Cytokines RNA Viral Cellular Structures and Organelles Pathogens Cellular Types medicine.drug Research Article Herpesviruses Stromal cell Papillomaviruses Immune Cells Immunology Blotting Western Biology Microbiology HPV-16 Cell Line 03 medical and health sciences Signs and Symptoms Extraction techniques Diagnostic Medicine medicine Genetics Epstein-Barr virus Humans Vesicles Antibody-Producing Cells Microbial Pathogens Cell Proliferation Inflammation Innate immune system Blood Cells lcsh:R Organisms Biology and Life Sciences Cell Biology Oncogene Proteins Viral Molecular Development Molecular biology Microvesicles RNA extraction Research and analysis methods Repressor Proteins 030104 developmental biology Cell culture Immune System Cytokine secretion lcsh:Q Interferons DNA viruses Developmental Biology |
| Zdroj: | PLoS ONE, 12(1). Public Library of Science PLoS ONE Aromseree, S, Middeldorp, J M, Pientong, C, van Eijndhoven, M, Ramayanti, O, Lougheed, S M, Pegtel, D M, Steenbergen, R D M & Ekalaksananan, T 2017, ' High Levels of EBV-Encoded RNA 1 (EBER1) Trigger Interferon and Inflammation-Related Genes in Keratinocytes Expressing HPV16 E6/E7 ', PLoS ONE, vol. 12, no. 1, pp. e0169290 . https://doi.org/10.1371/journal.pone.0169290 PLoS ONE, Vol 12, Iss 1, p e0169290 (2017) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0169290 |
| Popis: | Different types of cells infected with Epstein-Barr virus (EBV) can release exosomes containing viral components that functionally affect neighboring cells. Previously, we found that EBV was localized mostly in infiltrating lymphocytes within the stromal layer of cervical lesions. In this study, we aimed to determine effects of exosome-transferred EBV-encoded RNAs (EBERs) on keratinocytes expressing human papillomavirus (HPV) 16 E6/E7 (DonorI-HPV16 HFKs). Lipid transfection of in vitro-transcribed EBER1 molecules (ivt EBER1) into DonorI-HPV16 HFKs caused strong induction of interferon (IFN)-related genes and interleukin 6 (IL-6). To gain insights into the physiological situation, monocyte-derived dendritic cells (moDCs), low passage DonorI-HPV16 HFKs and primary keratinocytes were used as recipient cells for internalization of exosomes from wild-type EBV (wt EBV) or B95-8 EBV-infected lymphoblastoid cell lines (LCLs). qRT-PCR was used to determine the expression of EBER1, HPV16 E6/E7, IFN-related genes and IL-6 in recipient cells. The secretion of inflammatory cytokines was investigated using cytometric bead array. Wt EBV-modified exosomes induced both IFN-related genes and IL-6 upon uptake into moDCs, while exosomes from B95-8 EBV LCLs induced only IL-6 in moDCs. Internalization of EBV-modified exosomes was demonstrated in DonorI-HPV16 HFKs, yielding only EBER1 but not EBER2. However, EBER1 transferred by exosomes did not induce IFN-related genes or IL-6 expression and inflammatory cytokine secretion in DonorI-HPV16 HFKs and primary keratinocytes. EBER1 copy numbers in exosomes from wt EBV-infected LCLs were 10-fold higher than in exosomes from B95-8 LCLs (equal cell equivalent), whereas ivt EBER1 was used at approximately 100-fold higher concentration than in exosomes. These results demonstrated that the induction of IFN-related genes and IL-6 by EBER1 depends on quantity of EBER1 and type of recipient cells. High levels of EBER1 in cervical cells or infiltrating dendritic cells may play a role in the inflammation-to-oncogenesis transition of HPV-associated cervical cancer through modulation of innate immune signals. |
| Databáze: | OpenAIRE |
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