Identification of the novel K15 gene at the rightmost end of the Kaposi's sarcoma-associated herpesvirus genome

被引:83
作者
Choi, JK [1 ]
Lee, BS [1 ]
Shim, SN [1 ]
Li, MT [1 ]
Jung, JU [1 ]
机构
[1] Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Dept Microbiol & Mol Genet, Southborough, MA 01772 USA
关键词
D O I
10.1128/JVI.74.1.436-446.2000
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a distinct open reading frame called K15 at a position equivalent to the gene encoding LMP2A of Epstein-Barr virus (EBV), K15 isolates from body cavity-based lymphoma (BCBL) cells exhibited a dramatic sequence variation and a complex splicing pattern. However, all K15 alleles are organized similarly with the potential SH2 and SH3 binding moths in their cytoplasmic regions. Northern blot analysis showed that K15 was weakly expressed in latently infected BCBL-1 cells, and the level of its expression was significantly induced by tetradecanoyl phorbol acetate stimulation, K15 encoded 40- to 55-kDa proteins, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and was localized at the cytoplasm and plasma membrane. To demonstrate the signal-transducing activity of the K15 protein, we constructed a chimeric protein in which the cytoplasmic tail of the human CD8 alpha polypeptide was replaced with that of KSHV K15. While the CD8-K15 chimera was not capable of eliciting cellular signal transduction upon stimulation with an anti-CDS antibody, it significantly inhibited B-cell receptor signaling, as evidenced by a suppression of tyrosine phosphorylation and intracellular calcium mobilization, This inhibition required the putative SH2 or SH3 binding motif in the cytoplasmic region of K15. BiochemicaI study of CD8-K15 chimeras showed that the cytoplasmic region of K15 was constitutively tyrosine phosphorylated and that the tyrosine residue within the putative SH2 binding moth of K15 was a primary site of phosphorylation. These results demonstrate that KSHV K15 resembles LMP2A in genomic location, splicing pattern, and protein structure and by the presence of functional signal-transducing: motifs in the cytoplasmic region. Thus, KSHV K15 is likely a distant evolutionary relative of EBV LMP2A.
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页码:436 / 446
页数:11
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