Sequence polymorphisms between latent membrane proteins LMP1 and LMP2A do not correlate in EBV-associated reactive and malignant lympho-proliferations

Details

Serval ID
serval:BIB_9E157B1CD477
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Sequence polymorphisms between latent membrane proteins LMP1 and LMP2A do not correlate in EBV-associated reactive and malignant lympho-proliferations
Journal
International Journal of Cancer
Author(s)
Berger  C., Rothenberger  S., Bachmann  E., McQuain  C., Nadal  D., Knecht  H.
ISSN
0020-7136 (Print)
Publication state
Published
Issued date
05/1999
Volume
81
Number
3
Pages
371-5
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: May 5
Abstract
The latent membrane proteins LMP1 and LMP2A are co-expressed in most malignancies associated with Epstein-Barr virus (EBV). In contrast with the transforming LMP1 oncoprotein, LMP2A is expressed in lymphocytes of healthy EBV carriers and considered to maintain viral latency. Critical for these LMP2A functions are a transmembranous epitope recognized by specific cytotoxic T lymphocytes (CTLs) and the N-terminal immunoreceptor tyrosine-based activation motif (ITAM), blocking B-cell receptor signaling. To characterize ITAM and CTL motifs of LMP2A and to correlate them with C-terminal variants of LMP1 including the 30-bp deletion variant (LMP1delta), comparative sequence analysis was performed on 76 samples from patients with reactive and malignant lympho-proliferation (infectious mononucleosis, n=21; tonsillar hyperplasia, n=16, chronic lympho-proliferation, n = 9; Hodgkin's disease, n = 8; Non-Hodgkin's lymphoma, n = 5; AIDS-related large-cell lymphoma, n=17). The CTL motif was conserved in all but 2 cases (C426-->S). The ITAM motif was characterized by strictly conserved YXXL sequences in all cases, with a sequence polymorphism in between. The B95.8 prototype was found in 17% (13/76) of cases, while in 72% a variant with 3 point mutations (166796 C-->A, 166805 C-->A, 166810 C-->T) was detected; 11% had 1 or 2 of these mutations in addition to G-->A at 166793. In the C terminus of LMP1, a hypervariable region including LMP1delta was described in 61% of cases. There was no significant association of a particular LMP2A variant with either malignant phenotype or LMP1delta, demonstrating that the functional domains of LMP2A are conserved and that the sequence polymorphisms in LMP1 and LMP2A are independent.
Keywords
Conserved Sequence Epitopes, T-Lymphocyte Herpesviridae Infections/immunology/*virology *Herpesvirus 4, Human Humans Lymphoproliferative Disorders/immunology/*virology Polymorphism, Genetic T-Lymphocytes, Cytotoxic/immunology Tumor Virus Infections/immunology/*virology Viral Matrix Proteins/*chemistry/genetics
Pubmed
Web of science
Create date
25/01/2008 14:36
Last modification date
20/08/2019 15:04
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