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PMID: 12947043 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The EBV nuclear antigen 1 (EBNA1) enhances B cell immortalization several thousandfold.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 100 ·No. 19 ·2003-09-16 ·Pages 10989-94

Humme S, Reisbach G, Feederle R, Delecluse HJ, Bousset K, Hammerschmidt W, Schepers A

Abstract

The Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is one of the earliest viral proteins expressed after infection and is the only latent protein consistently expressed in viral-associated tumors. EBNA1's crucial role in viral DNA replication, episomal maintenance, and partitioning is well examined whereas its importance for the immortalization process and the tumorgenicity of EBV is unclear. To address these open questions, we generated, based on the maxi-EBV system, an EBNA1-deficient EBV mutant and used this strain to infect primary human B cells. Surprisingly, lymphoblastoid cell lines (LCL) emerged from these experiments, although with very low frequency. These cell lines were indistinguishable from normal LCLs with respect to proliferation and growth conditions. A detailed analysis indicated that the entire viral DNA was integrated into the cellular genome. At least 5 of the 11 latent EBV proteins were expressed, indicating the integrity of the EBV genome. EBNA1-positive and DeltaEBNA1-EBV-LCLs were injected into severe combined immunodeficient (SCID) mice to examine their tumorgenicity in comparison. Both groups supported tumor growth, indicating that EBNA1 is not mandatory for EBV's oncogenic potential. The results shown provide genetic evidence that EBNA1 is not essential to establish LCLs but promotes the efficiency of this process significantly.

MeSH Terms
B-Lymphocytes/cytology Blotting, Southern Blotting, Western Cell Line Cell Transformation, Viral/physiology DNA, Viral/analysis Epstein-Barr Virus Nuclear Antigens/physiology Herpesvirus 4, Human/genetics,physiology Humans In Situ Hybridization, Fluorescence Plasmids
Chemicals
DNA, Viral Epstein-Barr Virus Nuclear Antigens EBV-encoded nuclear antigen 1
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Humme Sibille
Department of Gene Vectors, GSF-National Research Center for Environment and Health, Marchioninistrasse 25, 81377 Munich, Germany.
Reisbach Gilbert
Feederle Regina
Delecluse Henri-Jacques
Bousset Kristine
Hammerschmidt Wolfgang
Schepers Aloys
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.1832776100
Published
2003-09-16
Epub
2003-00-28
Pages
10989-94
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC196914
Subset
IM
Grants
NCI NIH HHS · P01 CA022443 · United States
NCI NIH HHS · R01 CA070723 · United States
NCI NIH HHS · CA22443 · United States
NCI NIH HHS · CA70723 · United States
External Links
PubMed source DOI: 10.1073/pnas.1832776100 PMC Full Text View journal details
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