Epstein-Barr virus induces global changes in cellular mRNA isoform usage that are important for the maintenance of latency.

Homa, Nicholas J

Salinas, Raul

Forte, Eleonora

Robinson, Timothy J

Garcia-Blanco, Mariano A

Luftig, Micah A

2022-03-28T20:29:06Z

2022-03-28T20:29:06Z

2013-11

2022-03-28T20:29:06Z

Oncogenic viruses promote cell proliferation through the dramatic reorganization of host transcriptomes. In addition to regulating mRNA abundance, changes in mRNA isoform usage can have a profound impact on the protein output of the transcriptome. Using Epstein-Barr virus (EBV) transformation of primary B cells, we have studied the ability of an oncogenic virus to alter the mRNA isoform profile of its host. Using the algorithm called SplicerEX with two complementary Affymetrix microarray platforms, we uncovered 433 mRNA isoform changes regulated by EBV during B-cell transformation. These changes were largely orthogonal with the 2,163 mRNA abundance changes observed during transformation, such that less than one-third of mRNAs changing at the level of isoform also changed in overall abundance. While we observed no preference for a mechanistic class of mRNA isoform change, we detected a significant shortening of 3' untranslated regions and exclusion of cassette exons in EBV-transformed cells relative to uninfected B cells. Gene ontology analysis of the mRNA isoform changes revealed significant enrichment in nucleic acid binding proteins. We validated several of these isoform changes and were intrigued by those in two mRNAs encoding the proteins XBP1 and TCF4, which have both been shown to bind and activate the promoter of the major EBV lytic trans-activator BZLF1. Our studies indicate that EBV latent infection promotes the usage of mRNA isoforms of XBP1 and TCF4 that restrict BZLF1 activation. Therefore, characterization of global changes in mRNA isoform usage during EBV infection identifies a new mechanism for the maintenance of latent infection.

JVI.02464-13

0022-538X

1098-5514

https://hdl.handle.net/10161/24735

eng

American Society for Microbiology

Journal of virology

10.1128/jvi.02464-13

B-Lymphocytes

Humans

Herpesvirus 4, Human

Epstein-Barr Virus Infections

Cell Transformation, Viral

DNA-Binding Proteins

Trans-Activators

Transcription Factors

RNA, Messenger

RNA, Viral

Blotting, Western

Oligonucleotide Array Sequence Analysis

Gene Expression Profiling

Reverse Transcriptase Polymerase Chain Reaction

Virus Latency

Virus Replication

Gene Expression Regulation, Viral

Regulatory Sequences, Nucleic Acid

Basic Helix-Loop-Helix Leucine Zipper Transcription Factors

Promoter Regions, Genetic

Real-Time Polymerase Chain Reaction

RNA Isoforms

Biomarkers

Regulatory Factor X Transcription Factors

X-Box Binding Protein 1

Transcription Factor 4

Epstein-Barr virus induces global changes in cellular mRNA isoform usage that are important for the maintenance of latency.

Journal article

Salinas, Raul|0000-0001-9011-683X

Luftig, Micah A|0000-0002-2964-1907

12291

12301

22

Duke

School of Medicine

Staff

Basic Science Departments

Institutes and Centers

Biochemistry

Immunology

Molecular Genetics and Microbiology

Duke Cancer Institute

Published

87