English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Epstein-Barr virus (EBV) is a member of the γ-herpesvirus family estimated to infect 90% of the world’s adult population. Despite the high prevalence of infection, EBV-associated malignancies are largely kept in check by a strong cytotoxic T cell immune response. However, EBV causes lymphoproliferative disease in immune-deficient individuals following transplant and CNS and other lymphomas in HIV-infected individuals. EBV also plays a role in the pathogenesis of endemic African Burkitt’s lymphoma, Hodgkin’s disease, and nasopharyngeal carcinoma. In vitro, EBV infection of primary human B cells results in proliferation and outgrowth of indefinitely proliferating lymphoblastoid cell lines, or LCLs, which represent a viable model for the pathogenesis of EBV-associated malignancies.  Ongoing studies in our group have shown that the earliest EBV-infected proliferating B cells differ greatly from LCLs phenotypically. Using CFSE staining and flow cytometry-based sorting, we have isolated these early proliferating B cells and analyzed genome-wide exon level mRNA expression relative to uninfected resting B cells and LCLs. Gene ontology analysis of these expression data identified enrichment of genes associated with proliferation and the DNA damage response in early proliferation. Furthermore, c-Myc mRNA and activity, as inferred from its genome-wide expression signature, were also highly induced early.  Most interestingly, however, analysis of changes from early proliferating to final LCL outgrowth revealed striking attenuation of proliferative gene sets and c-Myc, along with delayed induction kinetics of NFκB activation. Specifically, genes with NFκB motifs in their promoters were highly expressed from early proliferating B cells to LCL and many canonical NFκB targets and pathway components were induced at late times after infection. These results suggest a novel, dynamic EBV-driven growth pattern and expression program that relies on mutually exclusive signals from c-Myc and NFκB. Furthermore, our data suggest that the earliest stages of EBV-driven B cell immortalization may provide unique insight into the pathogenesis of EBV-associated malignancies.

Global expression analysis of EBV-infected B cells early and late after infection reveals a dynamic interplay between growth and survival signals