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Analysis of Epstein-Barr virus-regulated host gene expression changes through primary B-cell outgrowth reveals delayed kinetics of latent membrane protein 1-mediated NF-κB activation.

Publication ,  Journal Article
Price, AM; Tourigny, JP; Forte, E; Salinas, RE; Dave, SS; Luftig, MA
Published in: J Virol
October 2012

Epstein-Barr virus (EBV) is an oncogenic human herpesvirus that dramatically reorganizes host gene expression to immortalize primary B cells. In this study, we analyzed EBV-regulated host gene expression changes following primary B-cell infection, both during initial proliferation and through transformation into lymphoblastoid cell lines (LCLs). While most EBV-regulated mRNAs were changed during the transition from resting, uninfected B cells through initial B-cell proliferation, a substantial number of mRNAs changed uniquely from early proliferation through LCL outgrowth. We identified constitutively and dynamically EBV-regulated biological processes, protein classes, and targets of specific transcription factors. Early after infection, genes associated with proliferation, stress responses, and the p53 pathway were highly enriched. However, the transition from early to long-term outgrowth was characterized by genes involved in the inhibition of apoptosis, the actin cytoskeleton, and NF-κB activity. It was previously thought that the major viral protein responsible for NF-κB activation, latent membrane protein 1 (LMP1), is expressed within 2 days after infection. Our data indicate that while this is true, LCL-level LMP1 expression and NF-κB activity are not evident until 3 weeks after primary B-cell infection. Furthermore, heterologous NF-κB activation during the first week after infection increased the transformation efficiency, while early NF-κB inhibition had no effect on transformation. Rather, inhibition of NF-κB was not toxic to EBV-infected cells until LMP1 levels and NF-κB activity were high. These data collectively highlight the dynamic nature of EBV-regulated host gene expression and support the notion that early EBV-infected proliferating B cells have a fundamentally distinct growth and survival phenotype from that of LCLs.

Duke Scholars

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

October 2012

Volume

86

Issue

20

Start / End Page

11096 / 11106

Location

United States

Related Subject Headings

  • Virus Replication
  • Virology
  • Viral Matrix Proteins
  • Tumor Suppressor Protein p53
  • RNA, Viral
  • RNA, Messenger
  • NF-kappa B
  • Humans
  • Herpesvirus 4, Human
  • Gene Expression Regulation
 

Citation

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Price, A. M., Tourigny, J. P., Forte, E., Salinas, R. E., Dave, S. S., & Luftig, M. A. (2012). Analysis of Epstein-Barr virus-regulated host gene expression changes through primary B-cell outgrowth reveals delayed kinetics of latent membrane protein 1-mediated NF-κB activation. J Virol, 86(20), 11096–11106. https://doi.org/10.1128/JVI.01069-12
Price, Alexander M., Jason P. Tourigny, Eleonora Forte, Raul E. Salinas, Sandeep S. Dave, and Micah A. Luftig. “Analysis of Epstein-Barr virus-regulated host gene expression changes through primary B-cell outgrowth reveals delayed kinetics of latent membrane protein 1-mediated NF-κB activation.J Virol 86, no. 20 (October 2012): 11096–106. https://doi.org/10.1128/JVI.01069-12.

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

October 2012

Volume

86

Issue

20

Start / End Page

11096 / 11106

Location

United States

Related Subject Headings

  • Virus Replication
  • Virology
  • Viral Matrix Proteins
  • Tumor Suppressor Protein p53
  • RNA, Viral
  • RNA, Messenger
  • NF-kappa B
  • Humans
  • Herpesvirus 4, Human
  • Gene Expression Regulation