Human cytomegalovirus early protein pUL21a promotes efficient viral DNA synthesis and the late accumulation of immediate-early transcripts

Journal of Virology

Volumn 85, Issue 2, 2011, Pages 663-674

  Fehr, Anthony R ^a   Yu, Dong ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

IMMEDIATE EARLY PROTEIN; IMMEDIATE EARLY PROTEIN PUL21A; UNCLASSIFIED DRUG; VIRUS DNA;

ARTICLE; CODON; CYTOMEGALOVIRUS; CYTOMEGALOVIRUS INFECTION; DNA SYNTHESIS; FIBROBLAST; GENE DELETION; GENE EXPRESSION; HUMAN; HUMAN CELL; PRIORITY JOURNAL; VIRION; VIROGENESIS; VIRUS INHIBITION; VIRUS MUTATION; VIRUS PARTICLE; VIRUS TRANSCRIPTION;

CELLS, CULTURED; CODON, NONSENSE; CYTOMEGALOVIRUS; DNA, VIRAL; FIBROBLASTS; GENE DELETION; GENE EXPRESSION REGULATION, VIRAL; GENETIC COMPLEMENTATION TEST; HUMANS; VIRAL PROTEINS; VIRUS REPLICATION;

HUMAN HERPESVIRUS 5;

EID: 78650671313     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.01599-10     Document Type: Article

References (73)

1. Arnoult, D., L. M. Bartle, A. Skaletskaya, D. Poncet, N. Zamzami, P. U. Park, J. Sharpe, R. J. Youle, and V. S. Goldmacher. 2004. Cytomegalovirus cell death suppressor vMIA blocks Bax- but not Bak-mediated apoptosis by binding and sequestering Bax at mitochondria. Proc. Natl. Acad. Sci. U. S. A. 101:7988-7993.
2. Borst, E. M., G. Hahn, U. H. Koszinowski, and M. Messerle. 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.
3. Chee, M. S., S. C. Satchwell, E. Preddie, K. M. Weston, and B. G. Barrell. 1990. Human cytomegalovirus encodes three G protein-coupled receptor homologues. Nature 344:774-777.
4. Child, S. J., M. Hakki, K. L. De Niro, and A. P. Geballe. 2004. Evasion of cellular antiviral responses by human cytomegalovirus TRS1 and IRS1. J. Virol. 78:197-205.
5. Child, S. J., S. Jarrahian, V. M. Harper, and A. P. Geballe. 2002. Complementation of vaccinia virus lacking the double-stranded RNA-binding protein gene E3L by human cytomegalovirus. J. Virol. 76:4912-4918.
6. Cuevas-Bennett, C., and T. Shenk. 2008. Dynamic histone H3 acetylation and methylation at human cytomegalovirus promoters during replication in fibroblasts. J. Virol. 82:9525-9536.
7. Dolan, A., C. Cunningham, R. D. Hector, A. F. Hassan-Walker, L. Lee, C. Addison, D. J. Dargan, D. J. McGeoch, D. Gatherer, V. C. Emery, P. D. Griffiths, C. Sinzger, B. P. McSharry, G. W. Wilkinson, and A. J. Davison. 2004. Genetic content of wild-type human cytomegalovirus. J. Gen. Virol. 85:1301-1312.
8. Dunn, W., C. Chou, H. Li, R. Hai, D. Patterson, V. Stolc, H. Zhu, and F. Liu. 2003. Functional profiling of a human cytomegalovirus genome. Proc. Natl. Acad. Sci. U. S. A. 100:14223-14228.
9. Dunn, W., P. Trang, Q. Zhong, E. Yang, C. van Belle, and F. Liu. 2005. Human cytomegalovirus expresses novel microRNAs during productive viral infection. Cell. Microbiol. 7:1684-1695.
10. Fehr, A. R., and D. Yu. 2010. Human cytomegalovirus gene UL21a encodes a short-lived cytoplasmic protein and facilitates virus replication in fibroblasts. J. Virol. 84:291-302.
11. Gawn, J. M., and R. F. Greaves. 2002. Absence of IE1 p72 protein function during low-multiplicity infection by human cytomegalovirus results in a broad block to viral delayed-early gene expression. J. Virol. 76:4441-4455.
12. Glass, M., A. Busche, K. Wagner, M. Messerle, and E. M. Borst. 2009. Conditional and reversible disruption of essential herpesvirus proteins. Nat. Methods 6:577-579.
13. Goldmacher, V. S., L. M. Bartle, A. Skaletskaya, C. A. Dionne, N. L. Kedersha, C. A. Vater, J. W. Han, R. J. Lutz, S. Watanabe, E. D. Cahir McFarland, E. D. Kieff, E. S. Mocarski, and T. Chittenden. 1999. A cytomegalovirus- encoded mitochondria-localized inhibitor of apoptosis structurally unrelated to Bcl-2. Proc. Natl. Acad. Sci. U. S. A. 96:12536-12541.
14. Greaves, R. F., and E. S. Mocarski. 1998. Defective growth correlates with reduced accumulation of a viral DNA replication protein after low-multiplicity infection by a human cytomegalovirus ie1 mutant. J. Virol. 72:366-379.
15. Grey, F., A. Antoniewicz, E. Allen, J. Saugstad, A. McShea, J. C. Carrington, and J. Nelson. 2005. Identification and characterization of human cytomegalovirus- encoded microRNAs. J. Virol. 79:12095-12099.
16. Groves, I. J., M. B. Reeves, and J. H. Sinclair. 2009. Lytic infection of permissive cells with human cytomegalovirus is regulated by an intrinsic 'pre-immediate-early' repression of viral gene expression mediated by histone post-translational modification. J. Gen. Virol. 90:2364-2374.
17. Hakki, M., E. E. Marshall, K. L. De Niro, and A. P. Geballe. 2006. Binding and nuclear relocalization of PKR by human cytomegalovirus TRS1
18. Heider, J. A., W. A. Bresnahan, and T. E. Shenk. 2002. Construction of a rationally designed human cytomegalovirus variant encoding a temperaturesensitive immediate-early 2 protein. Proc. Natl. Acad. Sci. U. S. A. 99:3141-3146.
19. Heineman, T. (ed.). 2007. Human cytomegalovirus vaccines. Cambridge University Press, Cambridge, United Kingdom.
20. Hwang, J., and R. F. Kalejta. 2007. Proteasome-dependent, ubiquitin-independent degradation of Daxx by the viral pp71 protein in human cytomegalovirus-infected cells. Virology 367:334-338.
21. Isomura, H., M. F. Stinski, A. Kudoh, S. Nakayama, T. Murata, Y. Sato, S. Iwahori, and T. Tsurumi. 2008. A cis element between the TATA box and the transcription start site of the major immediate-early promoter of human cytomegalovirus determines efficiency of viral replication. J. Virol. 82:849-858.
22. Juckem, L. K., K. W. Boehme, A. L. Feire, and T. Compton. 2008. Differential initiation of innate immune responses induced by human cytomegalovirus entry into fibroblast cells. J. Immunol. 180:4965-4977.
23. Jun, Y., E. Kim, M. Jin, H. C. Sung, H. Han, D. E. Geraghty, and K. Ahn. 2000. Human cytomegalovirus gene products US3 and US6 down-regulate trophoblast class I MHC molecules. J. Immunol. 164:805-811.
24. Khanna, R., and D. J. Diamond. 2006. Human cytomegalovirus vaccine: time to look for alternative options. Trends Mol. Med. 12:26-33.
25. Kinsella, T. M., and G. P. Nolan. 1996. Episomal vectors rapidly and stably produce high-titer recombinant retrovirus. Hum. Gene Ther. 7:1405-1413.
26. Kosz-Vnenchak, M., J. Jacobson, D. M. Coen, and D. M. Knipe. 1993. Evidence for a novel regulatory pathway for herpes simplex virus gene expression in trigeminal ganglion neurons. J. Virol. 67:5383-5393.
27. Kulesza, C. A., and T. Shenk. 2004. Human cytomegalovirus 5-kilobase immediate-early RNA is a stable intron. J. Virol. 78:13182-13189.
28. Landini, M. P., B. Severi, G. Furlini, and L. Badiali De Giorgi. 1987. Human cytomegalovirus structural components: intracellular and intraviral localization of p28 and p65-69 by immunoelectron microscopy. Virus Res. 8:15-23.
29. Marchini, A., H. Liu, and H. Zhu. 2001. Human cytomegalovirus with IE-2 (UL122) deleted fails to express early lytic genes. J. Virol. 75:1870-1878.
30. Marshall, E. E., C. J. Bierle, W. Brune, and A. P. Geballe. 2009. Essential role for either TRS1 or IRS1 in human cytomegalovirus replication. J. Virol. 83:4112-4120.
31. Mocarski, E. S., G. W. Kemble, J. M. Lyle, and R. F. Greaves. 1996. A deletion mutant in the human cytomegalovirus gene encoding IE1(491aa) is replication defective due to a failure in autoregulation. Proc. Natl. Acad. Sci. U. S. A. 93:11321-11326.
32. Mocarski, E. S., T. Shenk, and R. F. Pass (ed.). 2007. Cytomegaloviruses, 5th ed., vol. 2. Lippincott Williams & Wilkins, Philadelphia, PA.
33. Munger, J., S. U. Bajad, H. A. Coller, T. Shenk, and J. D. Rabinowitz. 2006. Dynamics of the cellular metabolome during human cytomegalovirus infection. PLoS Pathog. 2:e132.
34. Murphy, E., I. Rigoutsos, T. Shibuya, and T. E. Shenk. 2003. Reevaluation of human cytomegalovirus coding potential. Proc. Natl. Acad. Sci. U. S. A. 100:13585-13590.
35. Murphy, E., D. Yu, J. Grimwood, J. Schmutz, M. Dickson, M. A. Jarvis, G. Hahn, J. A. Nelson, R. M. Myers, and T. E. Shenk. 2003. Coding potential of laboratory and clinical strains of human cytomegalovirus. Proc. Natl. Acad. Sci. U. S. A. 100:14976-14981.
36. Nevels, M., W. Brune, and T. Shenk. 2004. SUMOylation of the human cytomegalovirus 72-kilodalton IE1 protein facilitates expression of the 86-kilodalton IE2 protein and promotes viral replication. J. Virol. 78:7803-7812.
37. Nevels, M., C. Paulus, and T. Shenk. 2004. Human cytomegalovirus immediate-early 1 protein facilitates viral replication by antagonizing histone deacetylation. Proc. Natl. Acad. Sci. U. S. A. 101:17234-17239.
38. Nichol, P. F., J. Y. Chang, E. M. Johnson, Jr., and P. D. Olivo. 1996. Herpes simplex virus gene expression in neurons: viral DNA synthesis is a critical regulatory event in the branch point between the lytic and latent pathways. J. Virol. 70:5476-5486.
39. Pari, G. S., and D. G. Anders. 1993. Eleven loci encoding trans-acting factors are required for transient complementation of human cytomegalovirus ori-Lyt-dependent DNA replication. J. Virol. 67:6979-6988.
40. Park, J. J., Y. E. Kim, H. T. Pham, E. T. Kim, Y. H. Chung, and J. H. Ahn. 2007. Functional interaction of the human cytomegalovirus IE2 protein with histone deacetylase 2 in infected human fibroblasts. J. Gen. Virol. 88:3214-3223.
41. Petrik, D. T., K. P. Schmitt, and M. F. Stinski. 2006. Inhibition of cellular DNA synthesis by the human cytomegalovirus IE86 protein is necessary for efficient virus replication. J. Virol. 80:3872-3883.
42. Puchtler, E., and T. Stamminger. 1991. An inducible promoter mediates abundant expression from the immediate-early 2 gene region of human cytomegalovirus at late times after infection. J. Virol. 65:6301-6306.
43. Qian, Z., B. Xuan, T. T. Hong, and D. Yu. 2008. The full-length protein encoded by human cytomegalovirus gene UL117 is required for the proper maturation of viral replication compartments. J. Virol. 82:3452-3465.
44. Reboredo, M., R. F. Greaves, and G. Hahn. 2004. Human cytomegalovirus proteins encoded by UL37 exon 1 protect infected fibroblasts against virusinduced apoptosis and are required for efficient virus replication. J. Gen. Virol. 85:3555-3567.
45. Reddehase, M. J., M. R. Fibi, G. M. Keil, and U. H. Koszinowski. 1986. Late-phase expression of a murine cytomegalovirus immediate-early antigen recognized by cytolytic T lymphocytes. J. Virol. 60:1125-1129.
46. Reeves, M., J. Murphy, R. Greaves, J. Fairley, A. Brehm, and J. Sinclair. 2006. Autorepression of the human cytomegalovirus major immediate-early promoter/enhancer at late times of infection is mediated by the recruitment of chromatin-remodeling enzymes by IE86. J. Virol. 80:9998-10009.
47. Reinhardt, B., P. Schaarschmidt, A. Bossert, A. Luske, G. Finkenzeller, T. Mertens, and D. Michel. 2005. Upregulation of functionally active vascular endothelial growth factor by human cytomegalovirus. J. Gen. Virol. 86:23-30.
48. Roizman, B., and P. E. Pellett. 2001. The family Herpesviridae: a brief introduction, p. 2381-2397. In D. M. Knipe, P. M. Howley, D. E. Griffin, R. A. Lamb, M. A. Martin, B. Roizman, and S. E. Straus (ed.), Fields virology, vol. 2. Lippincott-Raven, Philadelphia, PA.
49. Romanowski, M. J., and T. Shenk. 1997. Characterization of the human cytomegalovirus irs1 and trs1 genes: a second immediate-early transcription unit within irs1 whose product antagonizes transcriptional activation. J. Virol. 71:1485-1496.
50. Rupp, B., Z. Ruzsics, T. Sacher, and U. H. Koszinowski. 2005. Conditional cytomegalovirus replication in vitro and in vivo. J. Virol. 79:486-494.
51. Saffert, R. T., and R. F. Kalejta. 2007. Human cytomegalovirus gene expression is silenced by Daxx-mediated intrinsic immune defense in model latent infections established in vitro. J. Virol. 81:9109-9120.
52. Saffert, R. T., and R. F. Kalejta. 2006. Inactivating a cellular intrinsic immune defense mediated by Daxx is the mechanism through which the human cytomegalovirus pp71 protein stimulates viral immediate-early gene expression. J. Virol. 80:3863-3871.
53. + cells. J. Virol. 84:5594-5604.
54. Sanchez, V., K. D. Greis, E. Sztul, and W. J. Britt. 2000. Accumulation of virion tegument and envelope proteins in a stable cytoplasmic compartment during human cytomegalovirus replication: characterization of a potential site of virus assembly. J. Virol. 74:975-986.
55. Sanchez, V., A. K. McElroy, J. Yen, S. Tamrakar, C. L. Clark, R. A. Schwartz, and D. H. Spector. 2004. Cyclin-dependent kinase activity is required at early times for accurate processing and accumulation of the human cytomegalovirus UL122-123 and UL37 immediate-early transcripts and at later times for virus production. J. Virol. 78:11219-11232.
56. Sanchez, V., and D. H. Spector. 2008. Subversion of cell cycle regulatory pathways. Curr. Top. Microbiol. Immunol. 325:243-262.
57. Sanders, R. L., C. L. Clark, C. S. Morello, and D. H. Spector. 2008. Development of cell lines that provide tightly controlled temporal translation of the human cytomegalovirus IE2 proteins for complementation and functional analyses of growth-impaired and nonviable IE2 mutant viruses. J. Virol. 82:7059-7077.
58. Sanders, R. L., C. J. Del Rosario, E. A. White, and D. H. Spector. 2008. Internal deletions of IE2 86 and loss of the late IE2 60 and IE2 40 proteins encoded by human cytomegalovirus affect the levels of UL84 protein but not the amount of UL84 mRNA or the loading and distribution of the mRNA on polysomes. J. Virol. 82:11383-11397.
59. Schleiss, M. R. 2008. Cytomegalovirus vaccine development. Curr. Top. Microbiol. Immunol. 325:361-382.
60. Silva, M. C., Q. C. Yu, L. Enquist, and T. Shenk. 2003. Human cytomegalovirus UL99-encoded pp28 is required for the cytoplasmic envelopment of tegument-associated capsids. J. Virol. 77:10594-10605.
61. Smith, I. L., I. Taskintuna, F. M. Rahhal, H. C. Powell, E. Ai, A. J. Mueller, S. A. Spector, and W. R. Freeman. 1998. Clinical failure of CMV retinitis with intravitreal cidofovir is associated with antiviral resistance. Arch. Ophthalmol. 116:178-185.
62. Stenberg, R. M., A. S. Depto, J. Fortney, and J. A. Nelson. 1989. Regulated expression of early and late RNAs and proteins from the human cytomegalovirus immediate-early gene region. J. Virol. 63:2699-2708.
63. Stenberg, R. M., and M. F. Stinski. 1985. Autoregulation of the human cytomegalovirus major immediate-early gene. J. Virol. 56:676-682.
64. Stenberg, R. M., P. R. Witte, and M. F. Stinski. 1985. Multiple spliced and unspliced transcripts from human cytomegalovirus immediate-early region 2 and evidence for a common initiation site within immediate-early region 1. J. Virol. 56:665-675.
65. Stinski, M. F., and D. T. Petrik. 2008. Functional roles of the human cytomegalovirus essential IE86 protein. Curr. Top. Microbiol. Immunol. 325:133-152.
66. Stinski, M. F., D. R. Thomsen, R. M. Stenberg, and L. C. Goldstein. 1983. Organization and expression of the immediate early genes of human cytomegalovirus. J. Virol. 46:1-14.
67. Tenney, D. J., and A. M. Colberg-Poley. 1991. Expression of the human cytomegalovirus UL36-38 immediate early region during permissive infection. Virology 182:199-210.
68. Tenney, D. J., and A. M. Colberg-Poley. 1991. Human cytomegalovirus UL36-38 and US3 immediate-early genes: temporally regulated expression of nuclear, cytoplasmic, and polysome-associated transcripts during infection. J. Virol. 65:6724-6734.
69. Terhune, S., E. Torigoi, N. Moorman, M. Silva, Z. Qian, T. Shenk, and D. Yu. 2007. Human cytomegalovirus UL38 protein blocks apoptosis. J. Virol. 81:3109-3123.
70. White, E. A., C. L. Clark, V. Sanchez, and D. H. Spector. 2004. Small internal deletions in the human cytomegalovirus IE2 gene result in nonviable recombinant viruses with differential defects in viral gene expression. J. Virol.78:1817-1830.
71. White, E. A., C. J. Del Rosario, R. L. Sanders, and D. H. Spector. 2007. The IE2 60-kilodalton and 40-kilodalton proteins are dispensable for human cytomegalovirus replication but are required for efficient delayed early and late gene expression and production of infectious virus. J. Virol. 81:2573-2583.
72. Yu, D., M. C. Silva, and T. Shenk. 2003. Functional map of human cytomegalovirus AD169 defined by global mutational analysis. Proc. Natl. Acad. Sci. U. S. A. 100:12396-12401.
73. Yu, D., G. A. Smith, L. W. Enquist, and T. Shenk. 2002. Construction of a self-excisable bacterial artificial chromosome containing the human cytomegalovirus genome and mutagenesis of the diploid TRL/IRL13 gene. J. Virol. 76:2316-2328.