Document Detail


Epstein-Barr virus nuclear antigen 2 transactivates latent membrane protein LMP1.
MedLine Citation:
PMID:  2352328     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Several lines of evidence are compatible with the hypothesis that Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA-2) or leader protein (EBNA-LP) affects expression of the EBV latent infection membrane protein LMP1. We now demonstrate the following. (i) Acute transfection and expression of EBNA-2 under control of simian virus 40 or Moloney murine leukemia virus promoters resulted in increased LMP1 expression in P3HR-1-infected Burkitt's lymphoma cells and the P3HR-1 or Daudi cell line. (ii) Transfection and expression of EBNA-LP alone had no effect on LMP1 expression and did not act synergistically with EBNA-2 to affect LMP1 expression. (iii) LMP1 expression in Daudi and P3HR-1-infected cells was controlled at the mRNA level, and EBNA-2 expression in Daudi cells increased LMP1 mRNA. (iv) No other EBV genes were required for EBNA-2 transactivation of LMP1 since cotransfection of recombinant EBNA-2 expression vectors and genomic LMP1 DNA fragments enhanced LMP1 expression in the EBV-negative B-lymphoma cell lines BJAB, Louckes, and BL30. (v) An EBNA-2-responsive element was found within the -512 to +40 LMP1 DNA since this DNA linked to a chloramphenicol acetyltransferase reporter gene was transactivated by cotransfection with an EBNA-2 expression vector. (vi) The EBV type 2 EBNA-2 transactivated LMP1 as well as the EBV type 1 EBNA-2. (vii) Two deletions within the EBNA-2 gene which rendered EBV transformation incompetent did not transactivate LMP1, whereas a transformation-competent EBNA-2 deletion mutant did transactivate LMP1. LMP1 is a potent effector of B-lymphocyte activation and can act synergistically with EBNA-2 to induce cellular CD23 gene expression. Thus, EBNA-2 transactivation of LMP1 amplifies the biological impact of EBNA-2 and underscores its central role in EBV-induced growth transformation.
Authors:
F Wang; S F Tsang; M G Kurilla; J I Cohen; E Kieff
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of virology     Volume:  64     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  1990 Jul 
Date Detail:
Created Date:  1990-07-13     Completed Date:  1990-07-13     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  3407-16     Citation Subset:  IM; X    
Affiliation:
Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115.
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MeSH Terms
Descriptor/Qualifier:
Antigens, Viral / genetics*,  physiology*
B-Lymphocytes / physiology*
Blotting, Western
Cell Division
Cell Transformation, Viral
Cloning, Molecular
Epstein-Barr Virus Nuclear Antigens
Gene Expression Regulation, Viral*
Genes, Viral
Humans
Regulatory Sequences, Nucleic Acid
Trans-Activators / physiology*
Viral Matrix Proteins*
Viral Structural Proteins / genetics
Grant Support
ID/Acronym/Agency:
CA01395/CA/NCI NIH HHS; CA01417/CA/NCI NIH HHS; CA17006/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, Viral; 0/EBV-associated membrane antigen, Epstein-Barr virus; 0/Epstein-Barr Virus Nuclear Antigens; 0/Trans-Activators; 0/Viral Matrix Proteins; 0/Viral Structural Proteins
Comments/Corrections

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