Abstract
The EBV Latent Membrane Protein 2 (LMP2) may have a role in the establishment and maintenance of in vivo latency. The gene is transcribed into two mRNAs that produce two LMP2 protein isoforms. The LMP2a protein isoform has 12 transmembrane segments (TMs) and an amino terminal cytoplasmic signaling domain (CSD) while the LMP2b isoform is identical but lacks the CSD. There has not been a consensus on the cellular membrane localization being sometimes ascribed to either a plasma membrane or an intracellular location [M. Rovedo, R. Longnecker, J. Virol. 81:89–94, 2007; D. Lynch, J. Zimmerman, D.T. Rowe, J. Gen. Virol. 83:1025–1035, 2002; C. Dawson, J. George, S. Blake, R. Longnecker, L.S. Young, Virology 289:192–207, 2001]. Fluorescent marker and epitope tagged LMP2b truncation mutants progressively removing TMs from the N and C termini were used to assess the localization and aggregation properties of LMP2b. wtLMP2b had an exclusively intracellular perinuclear localization, while all truncations of the protein resulted in localization to the cell surface. By epitope loop-tagging, all the truncated LMP2b proteins were verified to be in the predicted membrane orientation. In co-transfection experiments, the C-terminal region was implicated in the self-aggregation properties of LMP2b. Thus, an intact 12 TM domain was required for intracellular localization and protein–protein interaction while a C-terminal region was responsible for auto-aggregative properties.
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References
A. Rickinson, E. Keiff, in Field’s Virology, ed. by B.N. Fields, D.M. Knipe, P.M. Howley (Lippincott-Raven Publishers, Philadelphia, PA, 1996), pp. 2397–2446
E. Miyashita, B. Yang, G. Babcock, D.A. Thorley-Lawson, J. Virol. 71, 4882 (1997)
R. Longnecker, in Human Tumor Virues, ed. by D. McCance (American Society for Microbiology, Washington, D.C., 1998), pp. 135–174
G. Laux, A. Economau, P.J. Farrell, J Gen Virol. 70(Pt 11), 3079 (1989)
M. Dykstra, R. Longnecker, S.K. Pierce, Immunity 14, 57 (2001)
A. Ikeda, R.G. Caldwell, R. Longnecker, M. Ikeda, J. Virol. 77, 5529 (2003)
R. Longnecker, B. Druker, T.M. Roberts, E. Kieff, J. Virol. 65, 3681 (1991)
A.L. Burkhardt, J.B. Bolen, E. Kieff, R. Longnecker, J. Virol. 66, 5161 (1992)
S. Fruehling, R. Swart, K.M. Dolwick, E. Kremmer, R. Longnecker, J. Virol. 72, 7796 (1998)
S. Fruehling, R. Longnecker, Virology 235, 241 (1997)
M. Merchant, R.G. Caldwell, R. Longnecker, J. Virol. 74, 9115 (2000)
M. Ikeda, A. Ikeda, R. Longnecker, Virology 300, 153 (2002)
G. Winberg, L. Matskova, F. Chen, P. Plant, D. Rotin, G. Gish, R. Ingham, I. Ernberg, T. Pawson, Mol. Cell Biol. 20, 8526 (2000)
P. Rivailler, C. Quink, F. Wang, J. Virol. 73, 8867 (1999)
P. Speck, K.A. Kline, P. Cheresh, R. Longnecker, J. Gen. Virol. 80(Pt 8), 2193 (1999)
R. Rochford, C.L. Miller, M.J. Cannon, K.M. Izumi, E. Kieff, R. Longnecker, Arch. Virol. 142(4), 707 (1997)
K. Konishi, S. Mauro, H. Kato, K. Takada, J. Gen. Virol. 82(Pt 6), 1451 (2001)
M. Rovedo, R. Longnecker, J. Virol. 81, 89 (2007)
M.D. Allen, L.S. Young, C.W. Dawson, J. Virol. 79, 1789 (2005)
D. Lynch, J. Zimmerman, D.T. Rowe, J. Gen. Virol. 83, 1025 (2002)
W. Mendenhall, R.J. Beaver, B.M. Beaver, Introduction to Probability and Statistics (Pacific Grove, Brooks/Cole Publishing Company, 1999)
C. Dawson, J. George, S. Blake, R. Longnecker, L.S. Young, Virology 289, 192 (2001)
L. Matskova, I. Ernberg, T. Pawson, G. Winberg, J. Virol. 75, 10941 (2001)
K. Colley, J. Glycobiol. 7, 1 (1997)
R. Longnecker, Adv. Cancer Res. 79, 175 (2000)
T. Kirchhausen, J. Pines, L. Toldo, F. Lafont, Curr. Opin. Cell Biol. 9, 473 (1997)
KK. Stanley, Mol. Membr. Biol. 13, 19 (1996)
M.R. Luke, F. Houghton, M.A. Perugini, P.A. Gleeson, Biochem. J. 388, 835 (2005)
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The authors would like to thank Dr. L. Kingsley for expert statistical advice.
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Tomaszewski-Flick, M.J., Rowe, D.T. Minimal protein domain requirements for the intracellular localization and self-aggregation of Epstein-Barr Virus Latent Membrane Protein 2. Virus Genes 35, 225–234 (2007). https://doi.org/10.1007/s11262-007-0118-8
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DOI: https://doi.org/10.1007/s11262-007-0118-8