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Journal of Virology, November 2006, p. 10787-10793, Vol. 80, No. 21
0022-538X/06/$08.00+0     doi:10.1128/JVI.01214-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

LMP1 Transmembrane Domain 1 and 2 (TM1-2) FWLY Mediates Intermolecular Interactions with TM3-6 To Activate NF-B

Vishal Soni, Teruhito Yasui, Ellen Cahir-McFarland, and Elliott Kieff^*

Channing Laboratory and Infectious Disease Division, Department of Medicine, Brigham and Women's Hospital, and Department of Microbiology and Molecular Genetics, Harvard Medical School and Harvard University, 181 Longwood Avenue, Boston, Massachusetts 02115

Received 9 June 2006/ Accepted 13 August 2006

The Epstein-Barr virus oncoprotein LMP1 has six transmembrane domains (TMs) that enable intermolecular aggregation and constitutive signaling through two C-terminal cytosolic domains. Expression of both TMs 1 and 2 without the C terminus (TM1-2C) and TMs 3 to 6 fused to the C terminus (TM3-6) results in partial association, which is substantially decreased by TM1 F₃₈WLY₄₁ mutation to A₃₈ALA₄₁. We now investigate whether TM1-2C can functionally interact with TM3-6. TM1-2C induced TM3-6 to mediate NF-B activation at 59% of LMP1 levels, and the effect was dependent on TM1-2 F₃₈WLY₄₁. TM1-2C even induced TM3-4 C terminus-mediated NF-B activation to 44% of LMP1 levels. Surprisingly, this effect was TM1 F₃₈WLY₄₁ independent, indicative of a role for TMs 5 and 6 in TM1 F₃₈WLY₄₁ effects. TM3 W₉₈ was also important for TM1-2C induction of TM3-6-mediated NF-B activation, for association, and for TM1 F₃₈WLY₄₁ dependence on C-terminal NF-B activation. These data support models in which the TM1 F₃₈WLY₄₁ effects are at least partially dependent on TM3 W₉₈ and a residue(s) in TMs 5 and 6.

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* Corresponding author. Mailing address: Channing Laboratory and Infectious Disease Division, Brigham and Women's Hospital, Boston, MA 02130. Phone: (617) 525-4263. Fax: (617) 525-4251. E-mail: ekieff{at}rics.bwh.harvard.edu.

Published ahead of print on 23 August 2006.

Present address: Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.

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Journal of Virology, November 2006, p. 10787-10793, Vol. 80, No. 21
0022-538X/06/$08.00+0     doi:10.1128/JVI.01214-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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