Modulation of T-cell receptor signal transduction by herpesvirus signaling adaptor protein.

Abstract:

:Because of its central regulatory role, T-cell receptor (TCR) signal transduction is a common target of viruses. We report here the identification of a small signaling protein, ORF5, of the T-lymphotropic tumor virus herpesvirus saimiri (HVS). ORF5 is predicted to contain 89 to 91 amino acids with an amino-terminal myristoylation site and six SH2 binding motifs, showing structural similarity to cellular LAT (linker for activation of T cells). Sequence analysis showed that, despite extensive sequence variation, the myristoylation site and SH2 binding motifs were completely conserved among 13 different ORF5 isolates. Upon TCR stimulation, ORF5 was efficiently tyrosine phosphorylated and subsequently interacted with cellular SH2-containing signaling proteins Lck, Fyn, SLP-76, and p85 through its tyrosine residues. ORF5 expression resulted in the marked augmentation of TCR signal transduction activity, evidenced by increased cellular tyrosine phosphorylation, intracellular calcium mobilization, CD69 surface expression, interleukin-2 production, and activation of the NF-AT, NF-kappa B, and AP-1 transcription factors. Despite its structural similarity to cellular LAT, however, ORF5 could only partially substitute for LAT function in TCR signal transduction. These results demonstrate that HVS utilizes a novel signaling protein, ORF5, to activate TCR signal transduction. This activation probably facilitates viral gene expression and, thereby, persistent infection.

journal_name

Mol Cell Biol

authors

Lee SH,Chung YH,Cho NH,Gwack Y,Feng P,Jung JU

doi

10.1128/MCB.24.12.5369-5382.2004

subject

Has Abstract

pub_date

2004-06-01 00:00:00

pages

5369-82

issue

12

eissn

0270-7306

issn

1098-5549

pii

24/12/5369

journal_volume

24

pub_type

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