The cytomegalovirus egress proteins pUL50 and pUL53 are translocated to the nuclear envelope through two distinct modes of nuclear import

Journal of General Virology

Volumn 94, Issue PART9, 2013, Pages 2056-2069

  Schmeiser, Cathrin ^a   Borst, Eva ^b   Sticht, Heinrich ^a   Marschall, Manfred ^a   Milbradt, Jens ^a  

^a UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

^b HANNOVER MEDICAL SCHOOL   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEIN PUL50; PROTEIN PUL53; UNCLASSIFIED DRUG; VIRUS PROTEIN;

AMINO ACID SUBSTITUTION; ARTICLE; CELL NUCLEUS MEMBRANE; CYTOMEGALOVIRUS; MUTANT; NONHUMAN; NUCLEAR EGRESS COMPLEX; NUCLEAR IMPORT; NUCLEAR LOCALIZATION SIGNAL; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; VIRUS CAPSID; VIRUS RECOMBINANT; WILD TYPE;

ACTIVE TRANSPORT, CELL NUCLEUS; AMINO ACID SUBSTITUTION; CELLS, CULTURED; CYTOMEGALOVIRUS; DNA MUTATIONAL ANALYSIS; FIBROBLASTS; HUMANS; MUTANT PROTEINS; NUCLEAR LOCALIZATION SIGNALS; PROTEIN INTERACTION MAPPING; VIRAL PROTEINS; VIRUS REPLICATION;

EID: 84881619516     PISSN: 00221317     EISSN: 14652099     Source Type: Journal    
DOI: 10.1099/vir.0.052571-0     Document Type: Article

References (58)

1. Adler, S. P., Nigro, G. & Pereira, L. (2007). Recent advances in the prevention and treatment of congenital cytomegalovirus infections. Semin Perinatol 31, 10-18.
2. Antonin, W., Ungricht, R. & Kutay, U. (2011). Traversing the NPC along the pore membrane: targeting of membrane proteins to the INM. Nucleus 2, 87-91.
3. Beck, M., Förster, F., Ecke, M., Plitzko, J. M., Melchior, F., Gerisch, G., Baumeister, W. & Medalia, O. (2004). Nuclear pore complex structure and dynamics revealed by cryoelectron tomography. Science 306, 1387-1390.
4. Borgese, N. & Fasana, E. (2011). Targeting pathways of C-tailanchored proteins. Biochim Biophys Acta 1808, 937-946.
5. Borgese, N., Colombo, S. & Pedrazzini, E. (2003). The tale of tailanchored proteins: coming from the cytosol and looking for a membrane. J Cell Biol 161, 1013-1019.
6. Borst, E. & Messerle, M. (2000). Development of a cytomegalovirus vector for somatic gene therapy. Bone Marrow Transplant 25 (Suppl 2), S80-S82.
7. Borst, E. M., Benkartek, C. & Messerle, M. (2007). Use of bacterial artificial chromosomes in generating targeted mutations in human and mouse cytomegaloviruses. Curr Protoc Immunol 77, 10.32.1-10.32.30.
8. Buchkovich, N. J., Maguire, T. G. & Alwine, J. C. (2010). Role of the endoplasmic reticulum chaperone BiP, SUN domain proteins, and dynein in altering nuclear morphology during human cytomegalovirus infection. J Virol 84, 7005-7017.
9. Camozzi, D., Pignatelli, S., Valvo, C., Lattanzi, G., Capanni, C., Dal Monte, P. & Landini, M. P. (2008). Remodelling of the nuclear lamina during human cytomegalovirus infection: role of the viral proteins pUL50 and pUL53. J Gen Virol 89, 731-740.
10. Fuchs, W., Klupp, B. G., Granzow, H., Osterrieder, N. & Mettenleiter, T. C. (2002). The interacting UL31 and UL34 gene products of pseudorabies virus are involved in egress from the host-cell nucleus and represent components of primary enveloped but not mature virions. J Virol 76, 364-378.
11. Furukawa, K., Panté, N., Aebi, U. & Gerace, L. (1995). Cloning of a cDNA for lamina-associated polypeptide 2 (LAP2) and identification of regions that specify targeting to the nuclear envelope. EMBO J 14, 1626-1636.
12. Furukawa, K., Fritze, C. E. & Gerace, L. (1998). The major nuclear envelope targeting domain of LAP2 coincides with its lamin binding region but is distinct from its chromatin interaction domain. J Biol Chem 273, 4213-4219.
13. Gonnella, R., Farina, A., Santarelli, R., Raffa, S., Feederle, R., Bei, R., Granato, M., Modesti, A., Frati, L. & other authors (2005). Characterization and intracellular localization of the Epstein-Barr virus protein BFLF2: interactions with BFRF1 and with the nuclear lamina. J Virol 79, 3713-3727.
14. Herget, T., Freitag, M., Morbitzer, M., Kupfer, R., Stamminger, T. & Marschall, M. (2004). Novel chemical class of pUL97 protein kinasespecific inhibitors with strong anticytomegaloviral activity. Antimicrob Agents Chemother 48, 4154-4162.
15. Holmer, L. & Worman, H. J. (2001). Inner nuclear membrane proteins: functions and targeting. Cell Mol Life Sci 58, 1741-1747.
16. Johnson, D. C. & Baines, J. D. (2011). Herpesviruses remodel host membranes for virus egress. Nat Rev Microbiol 9, 382-394.
17. Klupp, B. G., Granzow, H. & Mettenleiter, T. C. (2000). Primary envelopment of pseudorabies virus at the nuclear membrane requires the UL34 gene product. J Virol 74, 10063-10073.
18. Klupp, B. G., Granzow, H., Fuchs, W., Keil, G. M., Finke, S. & Mettenleiter, T. C. (2007). Vesicle formation from the nuclear membrane is induced by coexpression of two conserved herpesvirus proteins. Proc Natl Acad Sci U S A 104, 7241-7246.
19. Kosugi, S., Hasebe, M., Tomita, M. & Yanagawa, H. (2009). Systematic identification of cell cycle-dependent yeast nucleocytoplasmic shuttling proteins by prediction of composite motifs. Proc Natl Acad Sci U S A 106, 10171-10176.
20. Lake, C. M. & Hutt-Fletcher, L. M. (2004). The Epstein-Barr virus BFRF1 and BFLF2 proteins interact and coexpression alters their cellular localization. Virology 320, 99-106.
21. Lee, S. K. (1999). Four consecutive arginine residues at positions 836- 839 of EBV gp110 determine intracellular localization of gp110. Virology 264, 350-358.
22. Lee, C. P. & Chen, M. R. (2010). Escape of herpesviruses from the nucleus. Rev Med Virol 20, 214-230.
23. Lischka, P., Sorg, G., Kann, M., Winkler, M. & Stamminger, T. (2003). A nonconventional nuclear localization signal within the UL84 protein of human cytomegalovirus mediates nuclear import via the importin alpha/beta pathway. J Virol 77, 3734-3748.
24. Lötzerich, M., Ruzsics, Z. & Koszinowski, U. H. (2006). Functional domains of murine cytomegalovirus nuclear egress protein M53/p38. J Virol 80, 73-84.
25. Lusk, C. P., Blobel, G. & King, M. C. (2007). Highway to the inner nuclear membrane: rules for the road. Nat Rev Mol Cell Biol 8, 414-420.
26. Marschall, M., Helten, A., Hechtfischer, A., Zach, A., Banaschewski, C., Hell, W. & Meier-Ewert, H. (1999). The ORF, regulated synthesis, and persistence-specific variation of influenza C viral NS1 protein. Virology 253, 208-218.
27. Marschall, M., Freitag, M., Weiler, S., Sorg, G. & Stamminger, T. (2000). Recombinant green fluorescent protein-expressing human cytomegalovirus as a tool for screening antiviral agents. Antimicrob Agents Chemother 44, 1588-1597.
28. Marschall, M., Marzi, A., aus dem Siepen, P., Jochmann, R., Kalmer, M., Auerochs, S., Lischka, P., Leis, M. & Stamminger, T. (2005). Cellular p32 recruits cytomegalovirus kinase pUL97 to redistribute the nuclear lamina. J Biol Chem 280, 33357-33367.
29. Marschall, M., Feichtinger, S. & Milbradt, J. (2011). Regulatory roles of protein kinases in cytomegalovirus replication. Adv Virus Res 80, 69-101.
30. Mettenleiter, T. C., Klupp, B. G. & Granzow, H. (2009). Herpesvirus assembly: an update. Virus Res 143, 222-234.
31. Meyer, G. A. & Radsak, K. D. (2000). Identification of a novel signal sequence that targets transmembrane proteins to the nuclear envelope inner membrane. J Biol Chem 275, 3857-3866.
32. Meyer, G., Gicklhorn, D., Strive, T., Radsak, K. & Eickmann, M. (2002). A three-residue signal confers localization of a reporter protein in the inner nuclear membrane. Biochem Biophys Res Commun 291, 966-971.
33. Milbradt, J., Auerochs, S. & Marschall, M. (2007). Cytomegaloviral proteins pUL50 and pUL53 are associated with the nuclear lamina and interact with cellular protein kinase C. J Gen Virol 88, 2642-2650.
34. Milbradt, J., Auerochs, S., Sticht, H. & Marschall, M. (2009). Cytomegaloviral proteins that associate with the nuclear lamina: components of a postulated nuclear egress complex. J Gen Virol 90, 579-590.
35. Milbradt, J., Webel, R., Auerochs, S., Sticht, H. & Marschall, M. (2010). Novel mode of phosphorylation-triggered reorganization of the nuclear lamina during nuclear egress of human cytomegalovirus. J Biol Chem 285, 13979-13989.
36. Milbradt, J., Auerochs, S., Sevvana, M., Muller, Y. A., Sticht, H. & Marschall, M. (2012). Specific residues of a conserved domain in the N terminus of the human cytomegalovirus pUL50 protein determine its intranuclear interaction with pUL53. J Biol Chem 287, 24004-24016.
37. Mocarski, E. S., Shenk, T. & Pass, R. F. (2007). Cytomegaloviruses. In Fields Virology, pp. 2701-2772. Edited by D. M. Knipe & P. M. Howley. Philadelphia: Lippincott Williams & Wilkes.
38. Montpetit, B. & Weis, K. (2012). Cell biology. An alternative route for nuclear mRNP export by membrane budding. Science 336, 809-810.
39. Muranyi, W., Haas, J., Wagner, M., Krohne, G. & Koszinowski, U. H. (2002). Cytomegalovirus recruitment of cellular kinases to dissolve the nuclear lamina. Science 297, 854-857.
40. Nguyen Ba, A. N., Pogoutse, A., Provart, N. & Moses, A. M. (2009). NLStradamus: a simple Hidden Markov Model for nuclear localization signal prediction. BMC Bioinformatics 10, 202.
41. Ohba, T., Schirmer, E. C., Nishimoto, T. & Gerace, L. (2004). Energyand temperature-dependent transport of integral proteins to the inner nuclear membrane via the nuclear pore. J Cell Biol 167, 1051-1062.
42. Ostlund, C., Ellenberg, J., Hallberg, E., Lippincott-Schwartz, J. & Worman, H. J. (1999). Intracellular trafficking of emerin, the Emery- Dreifuss muscular dystrophy protein. J Cell Sci 112, 1709-1719.
43. Ott, M., Tascher, G., Hassdenteufel, S., Zimmermann, R., Haas, J. & Bailer, S. M. (2011). Functional characterization of the essential tail anchor of the herpes simplex virus type 1 nuclear egress protein pUL34. J Gen Virol 92, 2734-2745.
44. Paßvogel, L., Trü be, P., Schuster, F., Klupp, B. G. & Mettenleiter, T. C. (2013). Mapping of sequences in Pseudorabies virus pUL34 that are required for formation and function of the nuclear egress complex. J Virol 87, 4475-4485.
45. Reynolds, A. E., Ryckman, B. J., Baines, J. D., Zhou, Y., Liang, L. & Roller, R. J. (2001). U(L)31 and U(L)34 proteins of herpes simplex virus type 1 form a complex that accumulates at the nuclear rim and is required for envelopment of nucleocapsids. J Virol 75, 8803-8817.
46. Sam, M. D., Evans, B. T., Coen, D. M. & Hogle, J. M. (2009). Biochemical, biophysical, and mutational analyses of subunit interactions of the human cytomegalovirus nuclear egress complex. J Virol 83, 2996-3006.
47. Shikano, S. & Li, M. (2003). Membrane receptor trafficking: evidence of proximal and distal zones conferred by two independent endoplasmic reticulum localization signals. Proc Natl Acad Sci U S A 100, 5783-5788.
48. Smith, S. & Blobel, G. (1993). The first membrane spanning region of the lamin B receptor is sufficient for sorting to the inner nuclear membrane. J Cell Biol 120, 631-637.
49. Sorg, G. & Stamminger, T. (1999). Mapping of nuclear localization signals by simultaneous fusion to green fluorescent protein and to beta-galactosidase. Biotechniques 26, 858-862.
50. Soullam, B. & Worman, H. J. (1995). Signals and structural features involved in integral membrane protein targeting to the inner nuclear membrane. J Cell Biol 130, 15-27.
51. Tischer, B. K., von Einem, J., Kaufer, B. & Osterrieder, N. (2006). Two-step Red-mediated recombination for versatile high-efficiency markerless DNA manipulation in Escherichia coli. Biotechniques 40, 191-197.
52. Tischer, B. K., Smith, G. A. & Osterrieder, N. (2010). En passant mutagenesis: a two step markerless Red recombination system. Methods Mol Biol 634, 421-430.
53. Turgay, Y., Ungricht, R., Rothballer, A., Kiss, A., Csucs, G., Horvath, P. & Kutay, U. (2010). A classical NLS and the SUN domain contribute to the targeting of SUN2 to the inner nuclear membrane. EMBO J 29, 2262-2275.
54. Webel, R., Milbradt, J., Auerochs, S., Schregel, V., Held, C., Nöbauer, K., Razzazi-Fazeli, E., Jardin, C., Wittenberg, T. & other authors (2011). Two isoforms of the protein kinase pUL97 of human cytomegalovirus are differentially regulated in their nuclear translocation. J Gen Virol 92, 638-649.
55. Webel, R., Solbak, S. M. Ø., Held, C., Milbradt, J., Groß, A., Eichler, J., Wittenberg, T., Jardin, C., Sticht, H. & other authors (2012). Nuclear import of isoforms of the cytomegalovirus kinase pUL97 is mediated by differential activity of NLS1 and NLS2 both acting through classical importin-a binding. J Gen Virol 93, 1756-1768.
56. Wu, W., Lin, F. & Worman, H. J. (2002). Intracellular trafficking of MAN1, an integral protein of the nuclear envelope inner membrane. J Cell Sci 115, 1361-1371.
57. Yamauchi, Y., Shiba, C., Goshima, F., Nawa, A., Murata, T. & Nishiyama, Y. (2001). Herpes simplex virus type 2 UL34 protein requires UL31 protein for its relocation to the internal nuclear membrane in transfected cells. J Gen Virol 82, 1423-1428.
58. Zhu, H. Y., Yamada, H., Jiang, Y. M., Yamada, M. & Nishiyama, Y. (1999). Intracellular localization of the UL31 protein of herpes simplex virus type 2. Arch Virol 144, 1923-1935