Mutual interplay between the human cytomegalovirus terminase subunits pUL51, pUL56, and pUL89 promotes terminase complex formation

Journal of Virology

Volumn 91, Issue 12, 2017, Pages

  Neuber, Sebastian ^a   Wagner, Karen ^a   Goldner, Thomas ^b   Lischka, Peter ^b   Steinbrueck, Lars ^a   Messerle, Martin ^a,c   Borst, Eva Maria ^a  

^a HANNOVER MEDICAL SCHOOL   (Germany)

^b AiCuris GmbH   (Germany)

^c HELMHOLTZ CENTRE FOR INFECTION RESEARCH   (Germany)

Author keywords

Complex assembly; Cytomegalovirus; Nuclear import; Protein interactions; Protein stability; Terminase

Indexed keywords

HOLOENZYME; PROTEASOME; UNCLASSIFIED DRUG; VIRAL PROTEIN; VIRUS TERMINASE; DEOXYRIBONUCLEASE; TERMINASE; UL56 PROTEIN, CYTOMEGALOVIRUS; UL89 PROTEIN, CYTOMEGALOVIRUS; VIRUS DNA;

ARTICLE; BACTERIAL ARTIFICIAL CHROMOSOME; CELL NUCLEUS; CELLULAR DISTRIBUTION; COMPLEX FORMATION; CONTROLLED STUDY; ENZYME SUBUNIT; GENE DELETION; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; HUMAN CYTOMEGALOVIRUS; INHIBITION KINETICS; NONHUMAN; OPEN READING FRAME; PLASMID; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN FOLDING; PROTEIN LOCALIZATION; PROTEIN STABILITY; PROTEIN TRANSPORT; CELL LINE; CHEMISTRY; CYTOMEGALOVIRUS; ENZYMOLOGY; FIBROBLAST; GENETICS; HELA CELL LINE; METABOLISM; NUCLEOCYTOPLASMIC TRANSPORT; VIROLOGY; VIRUS GENOME;

ACTIVE TRANSPORT, CELL NUCLEUS; CELL LINE; CHROMOSOMES, ARTIFICIAL, BACTERIAL; CYTOMEGALOVIRUS; DNA, VIRAL; ENDODEOXYRIBONUCLEASES; FIBROBLASTS; GENOME, VIRAL; HELA CELLS; HUMANS; PROTEASOME ENDOPEPTIDASE COMPLEX; PROTEIN STABILITY; VIRAL PROTEINS; VIRAL STRUCTURAL PROTEINS;

EID: 85019718189     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.02384-16     Document Type: Article

References (71)

1. Casjens SR. 2011. The DNA-packaging nanomotor of tailed bacteriophages. Nat Rev Microbiol 9:647-657. https://doi.org/10.1038/nrmicro2632
2. Feiss M, Rao VB. 2012. The bacteriophage DNA packaging machine. Adv Exp Med Biol 726:489-509. https://doi.org/10.1007/978-1-4614-0980-9_22
3. Dittmer A, Drach JC, Townsend LB, Fischer A, Bogner E. 2005. Interaction of the putative human cytomegalovirus portal protein pUL104 with the large terminase subunit pUL56 and its inhibition by benzimidazole-Dribonucleosides. J Virol 79:14660-14667. https://doi.org/10.1128/JVI.79.23.14660-14667.2005
4. Bogner E, Radsak K, Stinski MF. 1998. The gene product of human cytomegalovirus open reading frame UL56 binds the pac motif and has specific nuclease activity. J Virol 72:2259-2264
5. Scheffczik H, Savva CG, Holzenburg A, Kolesnikova L, Bogner E. 2002. The terminase subunits pUL56 and pUL89 of human cytomegalovirus are DNA-metabolizing proteins with toroidal structure. Nucleic Acids Res 30:1695-1703. https://doi.org/10.1093/nar/30.7.1695
6. Couvreux A, Hantz S, Marquant R, Champier G, Alain S, Morellet N, Bouaziz S. 2010. Insight into the structure of the pUL89 C-terminal domain of the human cytomegalovirus terminase complex. Proteins 78:1520-1530. https://doi.org/10.1002/prot.22669
7. Nadal M, Mas PJ, Blanco AG, Arnan C, Sola M, Hart DJ, Coll M. 2010. Structure and inhibition of herpesvirus DNA packaging terminase nuclease domain. Proc Natl Acad Sci U S A 107:16078-16083. https://doi.org/10.1073/pnas.1007144107
8. Selvarajan Sigamani S, Zhao H, Kamau YN, Baines JD, Tang L. 2013. The structure of the herpes simplex virus DNA-packaging terminase pUL15 nuclease domain suggests an evolutionary lineage among eukaryotic and prokaryotic viruses. J Virol 87:7140-7148. https://doi.org/10.1128/JVI.00311-13
9. Visalli MA, House BL, Lahrman FJ, Visalli RJ. 2015. Intermolecular complementation between two varicella-zoster virus pORF30 terminase domains essential for DNA encapsidation. J Virol 89:10010-10022. https://doi.org/10.1128/JVI.01313-15
10. Hwang JS, Bogner E. 2002. ATPase activity of the terminase subunit pUL56 of human cytomegalovirus. J Biol Chem 277:6943-6948. https://doi.org/10.1074/jbc. M108984200
11. Scholz B, Rechter S, Drach JC, Townsend LB, Bogner E. 2003. Identification of the ATP-binding site in the terminase subunit pUL56 of human cytomegalovirus. Nucleic Acids Res 31:1426-1433. https://doi.org/10.1093/nar/gkg229
12. Walker JE, Saraste M, Runswick MJ, Gay NJ. 1982. Distantly related sequences in the alpha-and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold. EMBO J 1:945-951
13. Champier G, Hantz S, Couvreux A, Stuppfler S, Mazeron MC, Bouaziz S, Denis F, Alain S. 2007. New functional domains of human cytomegalovirus pUL89 predicted by sequence analysis and three-dimensional modelling of the catalytic site DEXDc. Antivir Ther 12:217-232
14. Wang JB, McVoy MA. 2008. Mutagenesis of the murine cytomegalovirus M56 terminase gene. J Gen Virol 89:2864-2868. https://doi.org/10.1099/vir.0.2008/003137-0
15. Sun S, Rao VB, Rossmann MG. 2010. Genome packaging in viruses. Curr Opin Struct Biol 20:114-120. https://doi.org/10.1016/j.sbi.2009.12.006
16. Petrov AS, Harvey SC. 2008. Packaging double-helical DNA into viral capsids: structures, forces, and energetics. Biophys J 95:497-502. https://doi.org/10.1529/biophysj.108.131797
17. Borst EM, Wagner K, Binz A, Sodeik B, Messerle M. 2008. The essential human cytomegalovirus gene UL52 is required for cleavage-packaging of the viral genome. J Virol 82:2065-2078. https://doi.org/10.1128/JVI.01967-07
18. Borst EM, Bauerfeind R, Binz A, Stephan TM, Neuber S, Wagner K, Steinbruck L, Sodeik B, Lenac RT, Jonjic S, Messerle M. 2016. The essential human cytomegalovirus proteins pUL77 and pUL93 are structural components necessary for viral genome encapsidation. J Virol 90:5860-5875. https://doi.org/10.1128/JVI.00384-16
19. Köppen-Rung P, Dittmer A, Bogner E. 2016. Intracellular distribution of capsid-associated pUL77 of human cytomegalovirus and interactions with packaging proteins and pUL93. J Virol 90:5876-5885. https://doi.org/10.1128/JVI.00351-16
20. DeRussy BM, Tandon R. 2015. Human cytomegalovirus pUL93 is required for viral genome cleavage and packaging. J Virol 89: 12221-12225. https://doi.org/10.1128/JVI.02382-15
21. DeRussy BM, Boland MT, Tandon R. 2016. Human cytomegalovirus pUL93 links nucleocapsid maturation and nuclear egress. J Virol 90: 7109-7117. https://doi.org/10.1128/JVI.00728-16
22. Borst EM, Kleine-Albers J, Gabaev I, Babic M, Wagner K, Binz A, Degenhardt I, Kalesse M, Jonjic S, Bauerfeind R, Messerle M. 2013. The human cytomegalovirus UL51 protein is essential for viral genome cleavagepackaging and interacts with the terminase subunits pUL56 and pUL89. J Virol 87:1720-1732. https://doi.org/10.1128/JVI.01955-12
23. Mocarski ES, Shenk T, Griffiths PD, Pass RF. 2013. Cytomegaloviruses, p 1960-2014. In Knipe DM, Howley PM (ed), Fields virology, 6th ed. Lippincott, Williams & Wilkins, Philadelphia, PA
24. Hakki M, Chou S. 2011. The biology of cytomegalovirus drug resistance. Curr Opin Infect Dis 24:605-611. https://doi.org/10.1097/QCO.0b013e32834cfb58
25. Bogner E. 2002. Human cytomegalovirus terminase as a target for antiviral chemotherapy. Rev Med Virol 12:115-127. https://doi.org/10.1002/rmv.344
26. Baines JD. 2011. Herpes simplex virus capsid assembly and DNA packaging: a present and future antiviral drug target. Trends Microbiol 19:606-613. https://doi.org/10.1016/j.tim.2011.09.001
27. Pi F, Zhao Z, Chelikani V, Yoder K, Kvaratskhelia M, Guo P. 2016. Development of potent antiviral drugs inspired by viral hexameric DNApackaging motors with revolving mechanism. J Virol 90:8036-8046. https://doi.org/10.1128/JVI.00508-16
28. Stoelben S, Arns W, Renders L, Hummel J, Muhlfeld A, Stangl M, Fischereder M, Gwinner W, Suwelack B, Witzke O, Durr M, Beelen DW, Michel D, Lischka P, Zimmermann H, Rubsamen-SchaeffH, Budde K. 2014. Preemptive treatment of cytomegalovirus infection in kidney transplant recipients with letermovir: results of a Phase 2a study. Transpl Int 27:77-86. https://doi.org/10.1111/tri.12225
29. Chemaly RF, Ullmann AJ, Stoelben S, Richard MP, Bornhauser M, Groth C, Einsele H, Silverman M, Mullane KM, Brown J, Nowak H, Kolling K, Stobernack HP, Lischka P, Zimmermann H, Rubsamen-SchaeffH, Champlin RE, Ehninger G. 2014. Letermovir for cytomegalovirus prophylaxis in hematopoietic-cell transplantation. N Engl J Med 370:1781-1789. https://doi.org/10.1056/NEJMoa1309533
30. Merck Sharp & Dohme. 19 October 2016. Merck announces pivotal phase 3 study of Letermovir, an investigational antiviral medicine for prevention of cytomegalovirus (CMV) infection in high-risk bone marrow transplant patients, met primary endpoint. Merck Sharp & Dohme, Kenilworth, NJ. http://www.mercknewsroom.com/news-release/corporate-news/merck-announces-pivotal-phase-3-study-letermovir-investigational-antivir
31. Goldner T, Hewlett G, Ettischer N, Ruebsamen-SchaeffH, Zimmermann H, Lischka P. 2011. The novel anticytomegalovirus compound AIC246 (Letermovir) inhibits human cytomegalovirus replication through a specific antiviral mechanism that involves the viral terminase. J Virol 85: 10884-10893. https://doi.org/10.1128/JVI.05265-11
32. Goldner T, Hempel C, Ruebsamen-SchaeffH, Zimmermann H, Lischka P. 2014. Geno-and phenotypic characterization of human cytomegalovirus mutants selected in vitro after letermovir (AIC246) exposure. Antimicrob Agents Chemother 58:610-613. https://doi.org/10.1128/AAC.01794-13
33. Chou S. 2015. Rapid in vitro evolution of human cytomegalovirus UL56 mutations that confer Letermovir resistance. Antimicrob Agents Chemother 59:6588-6593. https://doi.org/10.1128/AAC.01623-15
34. Lischka P, Michel D, Zimmermann H. 2016. Characterization of cytomegalovirus breakthrough events in a phase 2 prophylaxis trial of Letermovir (AIC246, MK 8228). J Infect Dis 213:23-30. https://doi.org/10.1093/infdis/jiv352
35. Lischka P, Hewlett G, Wunberg T, Baumeister J, Paulsen D, Goldner T, Ruebsamen-SchaeffH, Zimmermann H. 2010. In vitro and in vivo activities of the novel anticytomegalovirus compound AIC246. Antimicrob Agents Chemother 54:1290-1297. https://doi.org/10.1128/AAC.01596-09
36. Kaul DR, Stoelben S, Cober E, Ojo T, Sandusky E, Lischka P, Zimmermann H, Rubsamen-SchaeffH. 2011. First report of successful treatment of multidrug-resistant cytomegalovirus disease with the novel anti-CMV compound AIC246. Am J Transplant 11:1079-1084. https://doi.org/10.1111/j.1600-6143.2011.03530.x
37. Marschall M, Stamminger T, Urban A, Wildum S, Ruebsamen-SchaeffH, Zimmermann H, Lischka P. 2012. In vitro evaluation of the activities of the novel anticytomegalovirus compound AIC246 (letermovir) against herpesviruses and other human pathogenic viruses. Antimicrob Agents Chemother 56:1135-1137. https://doi.org/10.1128/AAC.05908-11
38. Dunn W, Chou C, Li H, Hai R, Patterson D, Stolc V, Zhu H, Liu F. 2003. Functional profiling of a human cytomegalovirus genome. Proc Natl Acad Sci U S A 100:14223-14228. https://doi.org/10.1073/pnas.2334032100
39. Yu D, Silva MC, Shenk T. 2003. Functional map of human cytomegalovirus AD169 defined by global mutational analysis. Proc Natl Acad Sci U S A 100:12396-12401. https://doi.org/10.1073/pnas.1635160100
40. Ruzsics Z, Borst EM, Bosse JB, Brune W, Messerle M. 2013. Manipulating CMV genomes by BAC mutagenesis: strategies and applications, p 38-58. In Reddehase MJ (ed), Cytomegaloviruses: from molecular pathogenesis to intervention, vol 1. Caister Academic Press, Norfolk, United Kingdom
41. Glass M, Busche A, Wagner K, Messerle M, Borst EM. 2009. Conditional and reversible disruption of essential herpesvirus proteins. Nat Methods 6:577-579. https://doi.org/10.1038/nmeth.1346
42. Wang JB, Zhu Y, McVoy MA, Parris DS. 2012. Changes in subcellular localization reveal interactions between human cytomegalovirus terminase subunits. Virol J 9:315. https://doi.org/10.1186/1743-422X-9-315
43. Uetz P, Dong YA, Zeretzke C, Atzler C, Baiker A, Berger B, Rajagopala SV, Roupelieva M, Rose D, Fossum E, Haas J. 2006. Herpesviral protein networks and their interaction with the human proteome. Science 311: 239-242. https://doi.org/10.1126/science.1116804
44. Fossum E, Friedel CC, Rajagopala SV, Titz B, Baiker A, Schmidt T, Kraus T, Stellberger T, Rutenberg C, Suthram S, Bandyopadhyay S, Rose D, von Brunn A, Uhlmann M, Zeretzke C, Dong YA, Boulet H, Koegl M, Bailer SM, Koszinowski U, Ideker T, Uetz P, Zimmer R, Haas J. 2009. Evolutionarily conserved herpesviral protein interaction networks. PLoS Pathog 5:e1000570. https://doi.org/10.1371/journal.ppat.1000570
45. Vizoso Pinto MG, Pothineni VR, Haase R, Woidy M, Lotz-Havla AS, Gersting SW, Muntau AC, Haas J, Sommer M, Arvin AM, Baiker A. 2011. Varicella zoster virus ORF25 gene product: an essential hub protein linking encapsidation proteins and the nuclear egress complex. J Proteome Res 10:5374-5382. https://doi.org/10.1021/pr200628s
46. Elbasani E, Gabaev I, Steinbrück L, Messerle M, Borst EM. 2014. Analysis of essential viral gene functions after highly efficient adenofection of cells with cloned human cytomegalovirus genomes. Viruses 6:354-370. https://doi.org/10.3390/v6010354
47. Thoma C, Borst E, Messerle M, Rieger M, Hwang JS, Bogner E. 2006. Identification of the interaction domain of the small terminase subunit pUL89 with the large subunit pUL56 of human cytomegalovirus. Biochemistry 45:8855-8863. https://doi.org/10.1021/bi0600796
48. Borst EM, Hahn G, Koszinowski UH, Messerle M. 1999. Cloning of the human cytomegalovirus (HCMV) genome as an infectious bacterial artificial chromosome in Escherichia coli: a new approach for construction of HCMV mutants. J Virol 73:8320-8329
49. Borst EM, Messerle M. 2000. Development of a cytomegalovirus vector for somatic gene therapy. Bone Marrow Transplant 25(Suppl 2):S80-S82
50. Tran K, Mahr JA, Spector DH. 2010. Proteasome subunits relocalize during human cytomegalovirus infection, and proteasome activity is necessary for efficient viral gene transcription. J Virol 84:3079-3093. https://doi.org/10.1128/JVI.02236-09
51. Salomons FA, Menendez-Benito V, Bottcher C, McCray BA, Taylor JP, Dantuma NP. 2009. Selective accumulation of aggregation-prone proteasome substrates in response to proteotoxic stress. Mol Cell Biol 29:1774-1785. https://doi.org/10.1128/MCB.01485-08
52. Giesen K, Radsak K, Bogner E. 2000. The potential terminase subunit of human cytomegalovirus, pUL56, is translocated into the nucleus by its own nuclear localization signal and interacts with importin alpha. J Gen Virol 81:2231-2244. https://doi.org/10.1099/0022-1317-81-9-2231
53. Sankhala RS, Lokareddy RK, Cingolani G. 2016. Divergent evolution of nuclear localization signal sequences in herpesvirus terminase subunits. J Biol Chem 291:11420-11433. https://doi.org/10.1074/jbc. M116.724393
54. Yang K, Baines JD. 2006. The putative terminase subunit of herpes simplex virus 1 encoded by UL28 is necessary and sufficient to mediate interaction between pUL15 and pUL33. J Virol 80:5733-5739. https://doi.org/10.1128/JVI.00125-06
55. Jacobson JG, Yang K, Baines JD, Homa FL. 2006. Linker insertion mutations in the herpes simplex virus type 1 UL28 gene: effects on UL28 interaction with UL15 and UL33 and identification of a second-site mutation in the UL15 gene that suppresses a lethal UL28 mutation. J Virol 80:12312-12323. https://doi.org/10.1128/JVI.01766-06
56. Yang K, Poon AP, Roizman B, Baines JD. 2008. Temperature-sensitive mutations in the putative herpes simplex virus type 1 terminase subunits pUL15 and pUL33 preclude viral DNA cleavage/packaging and interaction with pUL28 at the nonpermissive temperature. J Virol 82: 487-494. https://doi.org/10.1128/JVI.01875-07
57. Asher G, Reuven N, Shaul Y. 2006. 20S proteasomes and protein degradation "by default." Bioessays 28:844-849. https://doi.org/10.1002/bies.20447
58. Weekes MP, Tomasec P, Huttlin EL, Fielding CA, Nusinow D, Stanton RJ, Wang EC, Aicheler R, Murrell I, Wilkinson GW, Lehner PJ, Gygi SP. 2014. Quantitative temporal viromics: an approach to investigate hostpathogen interaction. Cell 157:1460-1472. https://doi.org/10.1016/j.cell.2014.04.028
59. Chari A, Fischer U. 2010. Cellular strategies for the assembly of molecular machines. Trends Biochem Sci 35:676-683. https://doi.org/10.1016/j.tibs.2010.07.006
60. Bolin LL, Hanson LK, Slater JS, Kerry JA, Campbell AE. 2010. Murine cytomegalovirus US22 protein pM140 protects its binding partner, pM141, from proteasome-dependent but ubiquitin-independent degradation. J Virol 84:2164-2168. https://doi.org/10.1128/JVI.01739-09
61. Clark E, Spector DH. 2015. Studies on the contribution of human cytomegalovirus UL21a and UL97 to viral growth and inactivation of the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase reveal a unique cellular mechanism for downmodulation of the APC/C subunits APC1, APC4, and APC5 J Virol 89:6928-6939
62. Balchin D, Hayer-Hartl M, Hartl FU. 2016. In vivo aspects of protein folding and quality control. Science 353:aac4354. https://doi.org/10.1126/science.aac4354
63. Hartl FU. 1996. Molecular chaperones in cellular protein folding. Nature 381:571-579. https://doi.org/10.1038/381571a0
64. Visalli RJ, Knepper J, Goshorn B, Vanover K, Burnside DM, Irven K, McGauley R, Visalli M. 2009. Characterization of the varicella-zoster virus ORF25 gene product: pORF25 interacts with multiple DNA encapsidation proteins. Virus Res 144:58-64. https://doi.org/10.1016/j.virusres.2009.03.019
65. Guo P, Lee TJ. 2007. Viral nanomotors for packaging of dsDNA and dsRNA. Mol Microbiol 64:886-903. https://doi.org/10.1111/j.1365-2958.2007.05706.x
66. Guo P, Noji H, Yengo CM, Zhao Z, Grainge I. 2016. Biological nanomotors with a revolution, linear, or rotation motion mechanism. Microbiol Mol Biol Rev 80:161-186. https://doi.org/10.1128/MMBR.00056-15
67. Savva CG, Holzenburg A, Bogner E. 2004. Insights into the structure of human cytomegalovirus large terminase subunit pUL56. FEBS Lett 563: 135-140. https://doi.org/10.1016/S0014-5793(04)00283-2
68. Tischer BK, Smith GA, Osterrieder N. 2010. En passant mutagenesis: a two step markerless red recombination system. Methods Mol Biol 634: 421-430. https://doi.org/10.1007/978-1-60761-652-8_30
69. Cherepanov PP, Wackernagel W. 1995. Gene disruption in Escherichia coli: TcR and KmR cassettes with the option of Flp-catalyzed excision of the antibiotic-resistance determinant. Gene 158:9-14. https://doi.org/10.1016/0378-1119(95)00193-A
70. Houston A, Williams JM, Rovis TL, Shanley DK, O'Riordan RT, Kiely PA, Ball M, Barry OP, Kelly J, Fanning A, MacSharry J, Mandelboim O, Singer BB, Jonjic S, Moore T. 2016. Pregnancy-specific glycoprotein expression in normal gastrointestinal tract and in tumors detected with novel monoclonal antibodies. MAbs 8:491-500. https://doi.org/10.1080/19420862.2015.1134410
71. Livak KJ, Schmittgen TD. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402-408. https://doi.org/10.1006/meth.2001.1262