EBV LMP-2A employs a novel mechanism to transactivate the HERV-K18 superantigen through its ITAM

Francis C. Hsiao, Albert K. Tai, Agnes Deglon, Natalie Sutkowski, Richard Longnecker, Brigitte T. Huber*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

EBV encodes latent membrane protein (LMP)-2A that functions as a homologue of the activated BCR. We have previously shown that LMP-2A transactivates a human endogenous retrovirus, HERV-K18, in infected B-lymphocytes. The Env protein of HERV-K18 encodes a superantigen that strongly stimulates a large number of T cells. To delineate the mechanism through which LMP-2A transactivates HERV-K18 env, we tested a panel of tyrosine mutants of LMP-2A in a murine B lymphoma that stably harbors HERV-K18. Our analysis revealed that the immunoreceptor tyrosine-based activation motif (ITAM) of LMP-2A is important for HERV-K18 env transactivation. ITAM contains 2 tyrosines that initiate signaling cascades when both residues are phosphorylated. However, in our study, single-tyrosine mutants of ITAM still retained full induction of HERV-K18 env. After truncating 25 kb of genomic sequence downstream of HERV-K18, LMP-2A failed to transactivate HERV-K18 env. Thus, an LMP-2A-inducible element is located downstream of HERV-K18.

Original languageEnglish (US)
Pages (from-to)261-266
Number of pages6
JournalVirology
Volume385
Issue number1
DOIs
StatePublished - Mar 1 2009

Keywords

  • EBV
  • HERV
  • ITAM
  • LMP-2A
  • Superantigen
  • Transcription

ASJC Scopus subject areas

  • Virology

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