Latent membrane protein 1of Epstein-Barr virus interacts with JAK3 and activates STAT proteins

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Abstract
Latent membrane protein 1 (LMP1) acts like a permanently activated receptor of the tumor necrosis factor (TNF)‐receptor superfamily and is absolutely required for B cell immortalization by Epstein–Barr virus. Molecular and biochemical approaches demonstrated that LMP1 usurps cellular signaling pathways resulting in the induction of NF‐κB and AP‐1 via two C‐terminal activating regions. We demonstrate here that a third region encompassing a proline rich sequence within the 33 bp repetitive stretch of LMP1's C‐terminus is required for the activation of Janus kinase 3 (JAK3). The interaction of LMP1 and JAK3 leads to the enhanced tyrosine auto/transphosphorylation of JAK3 within minutes after crosslinking of a conditional NGF‐R:LMP1 chimera and is a prerequisite for the activation of STAT transcription factors. These results reveal a novel activating region in the LMP1 C‐terminus and identify the JAK/STAT pathway as a target of this viral integral membrane protein in B cells.