| Autor: |
Wieland L; Department of Neurology, Medical Faculty, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany.; Department of Surgical and Conservative Pediatrics and Adolescent Medicine, Medical Faculty, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany., Schwarz T; Department of Neurology, Medical Faculty, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany., Engel K; Department of Surgical and Conservative Pediatrics and Adolescent Medicine, Medical Faculty, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany., Volkmer I; Department of Surgical and Conservative Pediatrics and Adolescent Medicine, Medical Faculty, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany., Krüger A; Department of Surgical and Conservative Pediatrics and Adolescent Medicine, Medical Faculty, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany., Tarabuko A; Department of Neurology, Medical Faculty, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany., Junghans J; Department of Neurology, Martha-Maria Hospital Halle-Dölau, 06120 Halle (Saale), Germany., Kornhuber ME; Department of Neurology, Medical Faculty, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany., Hoffmann F; Department of Neurology, Martha-Maria Hospital Halle-Dölau, 06120 Halle (Saale), Germany., Staege MS; Department of Surgical and Conservative Pediatrics and Adolescent Medicine, Medical Faculty, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany., Emmer A; Department of Neurology, Medical Faculty, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany. |
| Abstrakt: |
The immune pathogenesis of multiple sclerosis (MS) is thought to be triggered by environmental factors in individuals with an unfavorable genetic predisposition. Epstein-Barr virus (EBV) infection is a major risk factor for subsequent development of MS. Human endogenous retroviruses (HERVs) can be activated by EBV, and might be a missing link between an initial EBV infection and the later onset of MS. In this study, we investigated differential gene expression patterns in EBV-immortalized lymphoblastoid B cell lines (LCL) from MS-affected individuals (MSLCL) and controls by using RNAseq and qRT-PCR. RNAseq data from LCL mapped to the human genome and a virtual virus metagenome were used to identify possible biomarkers for MS or disease-relevant risk factors, e.g., the relapse rate. We observed that lytic EBNA-1 transcripts seemed to be negatively correlated with age leading to an increased expression in LCL from younger PBMC donors. Further, HERV-K (HML-2) GAG was increased upon EBV-triggered immortalization. Besides the well-known transactivation of HERV-K18, our results suggest that another six HERV loci are up-regulated upon stimulation with EBV. We identified differentially expressed genes in MSLCL, e.g., several HERV-K loci, ERVMER61-1 and ERV3-1, as well as genes associated with relapses. In summary, EBV induces genes and HERV in LCL that might be suitable as biomarkers for MS or the relapse risk. |
