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PMID: 8290598 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

An integral membrane protein (LMP2) blocks reactivation of Epstein-Barr virus from latency following surface immunoglobulin crosslinking.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 91 ·No. 2 ·1994-01-18 ·Pages 772-6

Miller CL, Lee JH, Kieff E, Longnecker R

Abstract

The role of latent membrane protein 2 (LMP2) in Epstein-Barr virus (EBV) infection was evaluated by using latently infected primary B lymphocytes that had been growth transformed by wild-type or specifically mutated EBV recombinants. LMP2 null mutant recombinant EBV-infected cells were similar to normal B lymphocytes in their rapid increase in intracellular free calcium after surface immunoglobulin crosslinking. These cells also became more permissive for lytic EBV replication. In sharp contrast, wild-type control infected cells had little or no increase in intracellular free calcium or in permissivity for EBV replication. The block to surface immunoglobulin crosslinking-induced permissivity in cells expressing wild-type LMP2 could be bypassed by raising intracellular free calcium levels with an ionophore and by activating protein kinase C with phorbol 12-myristate 13-acetate. LMP2A, not LMP2B, mediates this effect on calcium mobilization. Genetic and biochemical data are consistent with these effects being due to the interaction of the LMP2A N-terminal cytoplasmic domain with B lymphocyte src family tyrosine kinases.

MeSH Terms
Amino Acid Sequence Antigens, Viral/genetics,immunology Calcimycin/pharmacology Calcium/metabolism Capsid/immunology Cell Line, Transformed Cell Transformation, Viral Cross-Linking Reagents Herpesvirus 4, Human/genetics,immunology,physiology Humans Molecular Sequence Data Protein Kinase C/metabolism Receptors, Antigen, B-Cell/metabolism Tetradecanoylphorbol Acetate/pharmacology Viral Matrix Proteins/genetics,immunology Virus Activation/immunology Virus Replication/drug effects
Chemicals
Antigens, Viral Cross-Linking Reagents EBV-associated membrane antigen, Epstein-Barr virus Receptors, Antigen, B-Cell Viral Matrix Proteins Calcimycin Protein Kinase C Tetradecanoylphorbol Acetate Calcium
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Miller C L
Department of Medicine, Harvard Medical School, Boston, MA 02115.
Lee J H
Kieff E
Longnecker R
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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.91.2.772
Published
1994-01-18
Pages
772-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC43031
Subset
IM
Grants
NCI NIH HHS · CA 47006 · United States
External Links
PubMed source DOI: 10.1073/pnas.91.2.772 PMC Full Text View journal details
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