Inhibition of the Integrated stress response by Epstein-Barr virus oncoprotein LMP1 attenuates epithelial cell differentiation and lytic viral reactivation.

ABSTRACT: EBV infects normal oral keratinocytes (NOKs) and plays an essential role in undifferentiated nasopharyngeal carcinoma (NPC). We previously showed that the EBV oncogene, LMP1, promotes proliferation and inhibits spontaneous differentiation in telomerase-immortalized NOKs grown in growth factor-restricted conditions. Here we have further examined the phenotypes of NOKs infected with wild-type EBV (WT EBV) versus an LMP1-deleted EBV mutant (ΔLMP1 EBV) in growth factor-restricted conditions. RNA-seq results show that WT EBV-infected NOKs not only have reduced differentiation, but also decreased expression of genes activated by the integrated stress response (ISR) pathway, in comparison to the ΔLMP1 EBV-infected cells. The ISR pathway is mediated by increased phosphorylation of the eIF2α transl

SUBMITTER: Singh DR 

PROVIDER: S-EPMC11828382 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature