EBV, viruksen latenssiproteiini LMP1 ja epigenetiikka

https://dx.doi.org/10.3390%2Fpathogens10060763.

 LONG Covid muistuttaa  reaktivoitunutta  EBV-virusinfektiota.

https://pubmed.ncbi.nlm.nih.gov/20005943/

 (1)

. 2010 Feb;95(2):73-83.

doi: 10.1016/j.ygeno.2009.12.001. Epub 2009 Dec 18.

EBV transformation and cell culturing destabilizes DNA methylation in human lymphoblastoid cell lines

D Grafodatskaya  ¹ , S Choufani, J C Ferreira, D T Butcher, Y Lou, C Zhao, S W Scherer, R Weksberg

Affiliations

• PMID: 20005943
• DOI: 10.1016/j.ygeno.2009.12.001

Free article

Abstract

Recent research suggests that epigenetic alterations involving DNA methylation can be causative for neurodevelopmental, growth and metabolic disorders. Although lymphoblastoid cell lines have been an invaluable resource for the study of both genetic and epigenetic disorders, the impact of EBV transformation, cell culturing and freezing on epigenetic patterns is unknown. We compared genome-wide DNA methylation patterns of four white blood cell samples, four low-passage lymphoblastoid cell lines pre and post freezing and four high-passage lymphobastoid cell lines, using two microarray platforms: Illumina HumanMethylation27 platform containing 27,578 CpG sites and Agilent Human CpG island Array containing 27,800 CpG islands. Comparison of genome-wide methylation profiles between white blood cells and lymphoblastoid cell lines demonstrated methylation alterations in lymphoblastoid cell lines occurring at random genomic locations. These changes were more profound in high-passage cells. Freezing at low-passages did not have a significant effect on DNA methylation. Methylation changes were observed in several imprinted differentially methylated regions, including DIRAS3, NNAT, H19, MEG3, NDN and MKRN3, but not in known imprinting centers. Our results suggest that lymphoblastoid cell lines should be used with caution for the identification of disease-associated DNA methylation changes or for discovery of new imprinted genes, as the methylation patterns seen in these cell lines may not always be representative of DNA methylation present in the original B-lymphocytes of the patient.

2009 Elsevier Inc. All rights reserved. 

(2) 

. 2009 Jun;19(3):158-64.

doi: 10.1016/j.semcancer.2009.02.012. Epub 2009 Feb 24.

Epigenetic dysregulation of the host cell genome in Epstein-Barr virus-associated neoplasia

Hans Helmut Niller  ¹ , Hans Wolf, Janos Minarovits

Affiliations

• PMID: 19429479
• DOI: 10.1016/j.semcancer.2009.02.012

Abstract

Epstein-Barr virus (EBV), a human herpesvirus, is associated with a wide variety of malignant tumors. The expression of the latent viral RNAs is under strict, host-cell dependent transcriptional control. This results in an almost complete transcriptional silencing of the EBV genome in memory B-cells. In tumor cells, germinal center B-cells and lymphoblastoid cells, distinct viral latency promoters are active. Epigenetic mechanisms contribute to this strict control. In EBV-infected cells, epigenetic mechanisms also alter the expression of cellular genes, including tumor suppressor genes. In Nasopharyngeal Carcinoma, the hypermethylation of certain cellular promoters is attributed to the upregulation of DNA methyltransferases by the viral oncoprotein LMP1 (latent membrane protein 1) via JNK/AP1-signaling. The role of other viral latency products in the epigenetic dysregulation of the cellular genome remains to be established. Analysis of epigenetic alterations in EBV-associated neoplasms may result in a better understanding of their pathogenesis and may facilitate the development of new therapies.