Understanding Epstein-barr virus life cycle with proteomics: A temporal analysis of ubiquitination during virus reactivation

Dong Wen Lv, Jun Zhong, Kun Zhang, Akhilesh Pandey, Renfeng Li

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Epstein-Barr virus (EBV) is a human γ-herpesvirus associated with cancer, including Burkitt lymphoma, nasopharyngeal, and gastric carcinoma. EBV reactivation in latently infected B cells is essential for persistent infection whereby B cell receptor (BCR) activation is a physiologically relevant stimulus. Yet, a global view of BCR activation-regulated protein ubiquitination is lacking when EBV is actively replicating. We report here, for the first time, the long-term effects of IgG cross-linking-regulated protein ubiquitination and offer a basis for dissecting the cellular environment during the course of EBV lytic replication. Using the Akata-BX1 (EBV+) and Akata-4E3 (EBV-) Burkitt lymphoma cells, we monitored the dynamic changes in protein ubiquitination using quantitative proteomics. We observed temporal alterations in the level of ubiquitination at ∼150 sites in both EBV+ and EBV- B cells post-IgG cross-linking, compared with controls with no cross-linking. The majority of protein ubiquitination was downregulated. The upregulated ubiquitination events were associated with proteins involved in RNA processing. Among the downregulated ubiquitination events were proteins involved in apoptosis, ubiquitination, and DNA repair. These comparative and quantitative proteomic observations represent the first analysis on the effects of IgG cross-linking at later time points when the majority of EBV genes are expressed and the viral genome is actively being replicated. In all, these data enhance our understanding of mechanistic linkages connecting protein ubiquitination, RNA processing, apoptosis, and the EBV life cycle.

Original languageEnglish (US)
Pages (from-to)27-37
Number of pages11
JournalOMICS A Journal of Integrative Biology
Volume21
Issue number1
DOIs
StatePublished - Jan 1 2017
Externally publishedYes

Fingerprint

Ubiquitination
Life Cycle Stages
Human Herpesvirus 4
Viruses
Proteomics
Life cycle
B-Lymphocytes
Proteins
Burkitt Lymphoma
Immunoglobulin G
Cells
Down-Regulation
Genes
Chemical activation
RNA
Apoptosis
Viral Genome
Herpesviridae
Virus Replication
Processing

Keywords

  • Association Study
  • big data
  • proteomics

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Understanding Epstein-barr virus life cycle with proteomics : A temporal analysis of ubiquitination during virus reactivation. / Lv, Dong Wen; Zhong, Jun; Zhang, Kun; Pandey, Akhilesh; Li, Renfeng.

In: OMICS A Journal of Integrative Biology, Vol. 21, No. 1, 01.01.2017, p. 27-37.

Research output: Contribution to journalArticle

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