Ribosome Protein L4 is essential for Epstein-Barr Virus Nuclear Antigen 1 function.

Abstract

Epstein-Barr Virus (EBV) Nuclear Antigen 1 (EBNA1)-mediated origin of plasmid replication (oriP) DNA episome maintenance is essential for EBV-mediated tumorigenesis. We have now found that EBNA1 binds to Ribosome Protein L4 (RPL4). RPL4 shRNA knockdown decreased EBNA1 activation of an oriP luciferase reporter, EBNA1 DNA binding in lymphoblastoid cell lines, and EBV genome number per lymphoblastoid cell line. EBV infection increased RPL4 expression and redistributed RPL4 to cell nuclei. RPL4 and Nucleolin (NCL) were a scaffold for an EBNA1-induced oriP complex. The RPL4 N terminus cooperated with NCL-K429 to support EBNA1 and oriP-mediated episome binding and maintenance, whereas the NCL C-terminal K380 and K393 induced oriP DNA H3K4me2 modification and promoted EBNA1 activation of oriP-dependent transcription. These observations provide new insights into the mechanisms by which EBV uses NCL and RPL4 to establish persistent B-lymphoblastoid cell infection.

• Authors: Chih-Lung Shen, Cheng-Der Liu, Ren-In You, Yung-Hao Ching, Jun Liang, Liangru Ke, Ya-Lin Chen, Hong-Chi Chen, Hao-Jen Hsu, Je-Wen Liou, Elliott Kieff, Chih-Wen Peng
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 113 Issue 8 Pg. 2229-34 (Feb 23 2016) ISSN: 1091-6490 [Electronic] United States
• PMID: 26858444 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Viral
• Epstein-Barr Virus Nuclear Antigens
• Phosphoproteins
• RNA, Small Interfering
• RNA-Binding Proteins
• Ribosomal Proteins
• ribosomal protein L4
• EBV-encoded nuclear antigen 1

Topics

• B-Lymphocytes (metabolism, virology)
• Cell Line
• DNA, Viral (genetics, metabolism)
• Epstein-Barr Virus Nuclear Antigens (genetics, metabolism)
• Gene Knockdown Techniques
• Genome, Viral
• Herpesvirus 4, Human (genetics, metabolism, pathogenicity)
• Host-Pathogen Interactions
• Humans
• Phosphoproteins (genetics, metabolism)
• Plasmids (genetics, metabolism)
• RNA, Small Interfering (genetics)
• RNA-Binding Proteins (genetics, metabolism)
• Replication Origin
• Ribosomal Proteins (antagonists & inhibitors, genetics, metabolism)
• Transcriptional Activation
• Nucleolin