EBV LMP-2A employs a novel mechanism to transactivate the HERV-K18 superantigen through its ITAM.
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.
Hsiao
Francis C
FC
Department of Pathology, Tufts University School of Medicine, Boston, MA 02111, USA.
Tai
Albert K
AK
Deglon
Agnes
A
Sutkowski
Natalie
N
Longnecker
Richard
R
Huber
Brigitte T
BT
D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000821:virology; D045744:Cell Line, Tumor; D020077:Endogenous Retroviruses / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D007376:Interleukin-2 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D018089:Superantigens / Q000378:metabolism*; D015533:Transcriptional Activation; D014763:Viral Matrix Proteins / Q000378:metabolism*; D014775:Virus Activation / Q000502:physiology*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; C107453:ERVK-18 protein, human; D007376:Interleukin-2; D008565:Membrane Proteins; D018089:Superantigens; D014763:Viral Matrix Proteins