Alternative splicing of the human cytomegalovirus major immediate-early genes affects infectious-virus replication and control of cellular cyclin-dependent kinase

Journal of Virology

Volumn 85, Issue 2, 2011, Pages 804-817

  Du, Guixin ^a   Dutta, Nirmal ^a   Lashmit, Philip ^a   Stinski, Mark F ^a  

^a UNIVERSITY OF IOWA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIN DEPENDENT KINASE 1; MESSENGER RNA; VIRUS DNA; VIRUS PROTEIN;

ALTERNATIVE RNA SPLICING; ARTICLE; CELL CYCLE; CELL CYCLE G2 PHASE; CELL CYCLE M PHASE; CELL CYCLE S PHASE; CHROMATIN CONDENSATION; DNA SYNTHESIS; ENZYME ACTIVITY; EXON; GENE EXPRESSION; GENE MUTATION; HUMAN; HUMAN CELL; HUMAN CYTOMEGALOVIRUS; IMMEDIATE EARLY GENE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; VIROGENESIS; VIRUS INFECTIVITY; VIRUS REPLICATION;

ALTERNATIVE SPLICING; CDC2 PROTEIN KINASE; CELL CYCLE; CELLS, CULTURED; CYTOMEGALOVIRUS; DNA, VIRAL; GENE EXPRESSION REGULATION, VIRAL; GENES, IMMEDIATE-EARLY; GENETIC COMPLEMENTATION TEST; HUMANS; MUTATION; RNA, MESSENGER; RNA, VIRAL; VIRAL PROTEINS; VIRUS REPLICATION;

HUMAN HERPESVIRUS 5;

EID: 78650675148     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.01173-10     Document Type: Article

References (74)

1. Ahn, J. H., E. J. Brignole III, and G. S. Hayward. 1998. Disruption of PML subnuclear domains by the acidic IE1 protein of human cytomegalovirus is mediated through interaction with PML and may modulate a RING fingerdependent cryptic transactivator function of PML. Mol. Cell. Biol. 18:4899-4913.
2. Awasthi, S., J. A. Isler, and J. C. Alwine. 2004. Analysis of splice variants of the immediate-early 1 region of human cytomegalovirus. J. Virol. 78:8191-8200.
3. Balvay, L., D. Libri, and M. Y. Fiszman. 1993. Pre-mRNA secondary structure and the regulation of splicing. Bioessays 15:165-169.
4. Baracchini, E., E. Glezer, K. Fish, R. M. Stenberg, J. A. Nelson, and P. Ghazal. 1992. An isoform variant of the cytomegalovirus immediate-early auto repressor functions as a transcriptional activator. Virology 188:518-529.
5. Browne, E. P., B. Wing, D. Coleman, and T. Shenk. 2001. Altered cellular mRNA levels in human cytomegalovirus-infected fibroblasts: viral block to the accumulation of antiviral mRNAs. J. Virol. 75:12319-12330.
6. Buratti, E., and F. E. Baralle. 2004. Influence of RNA secondary structure on the pre-mRNA splicing process. Mol. Cell. Biol. 24:10505-10514.
7. Castillo, J. P., A. D. Yurochko, and T. F. Kowalik. 2000. Role of human cytomegalovirus immediate-early proteins in cell growth control. J. Virol. 74:8028-8037.
8. Caswell, R., C. Hagemeier, C. J. Chiou, G. Hayward, T. Kouzarides, and J. Sinclair. 1993. The human cytomegalovirus 86K immediate early (IE) 2 protein requires the basic region of the TATA-box binding protein (TBP) for binding, and interacts with TBP and transcription factor TFIIB via regions of IE2 required for transcriptional regulation. J. Gen. Virol. 74:2691-2698.
9. Cherrington, J. M., E. L. Khoury, and E. S. Mocarski. 1991. Human cytomegalovirus ie2 negatively regulates alpha gene expression via a short target sequence near the transcription start site. J. Virol. 65:887-896.
10. 1/S transition. J. Virol. 71:1629-1634.
11. 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.
12. Ellis, H. M., D. Yu, T. DiTizio, and D. L. Court. 2001. High efficiency mutagenesis, repair, and engineering of chromosomal DNA using singlestranded oligonucleotides. Proc. Natl. Acad. Sci. U. S. A. 98:6742-6746.
13. Fortunato, E. A., V. Sanchez, J. Y. Yen, and D. H. Spector. 2002. Infection of cells with human cytomegalovirus during S phase results in a blockade to immediate-early gene expression that can be overcome by inhibition of the proteasome. J. Virol. 76:5369-5379.
14. Gaspar, M., and T. Shenk. 2006. Human cytomegalovirus inhibits a DNA damage response by mislocalizing checkpoint proteins. Proc. Natl. Acad. Sci. U. S. A. 103:2821-2826.
15. 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.
16. Graham, F. L., and A. J. van der Eb. 1973. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology 52:456-467.
17. Greaves, R. F., and E. S. Mocarski. 1998. Defective growth correlates with reduced accumulation of a viral DNA replication protein after lo w-multiplicity infection by a human cytomegalovirus ie1 mutant. J. Virol. 72:366-379.
18. Hagemeier, C., R. Caswell, G. Hayhurst, J. Sinclair, and T. Kouzarides. 1994. Functional interaction between the HCMV IE2 transactivator and the retinoblastoma protein. EMBO J. 13:2897-2903.
19. Hagemeier, C., S. Walker, R. Caswell, T. Kouzarides, and J. Sinclair. 1992. The human cytomegalovirus 80-kilodalton but not the 72-kilodalton immediate- early protein transactivates heterologous promoters in a TATA boxdependent mechanism and interacts directly with TFIID. J. Virol. 66:4452-4456.
20. Hayashi, M. L., C. Blankenship, and T. Shenk. 2000. Human cytomegalovirus UL69 protein is required for efficient accumulation of infected cells in the G1 phase of the cell cycle. Proc. Natl. Acad. Sci. U. S. A. 97:2692-2696.
21. Hertel, L., S. Chou, and E. S. Mocarski. 2007. Viral and cell cycle-regulated kinases in cytomegalovirus-induced pseudomitosis and replication. PLoS Pathog. 3:e6.
22. Hertel, L., and E. S. Mocarski. 2004. Global analysis of host cell gene expression late during cytomegalovirus infection reveals extensive dysregulation of cell cycle gene expression and induction of pseudomitosis indepe ndentof US28 function. J. Virol. 78:11988-12011.
23. Huh, Y. H., Y. E. Kim, E. T. Kim, J. J. Park, M. J. Song, H. Zhu, G. S. Hayward, and J. H. Ahn. 2008. Binding STAT2 by the acidic domain of human cytomegalovirus IE1 promotes viral growth and is negatively regulated by SUMO. J. Virol. 82:10444-10454.
24. Hume, A. J., J. S. Finkel, J. P. Kamil, D. M. Coen, M. R. Culbertson, and R. F. Kalejta. 2008. Phosphorylation of retinoblastoma protein by viral protein with cyclin-dependent kinase function. Science 320:797-799.
25. Isomura, H., M. F. Stinski, A. Kudoh, T. Daikoku, N. Shirata, and T. Tsurumi. 2005. Two Sp1/Sp3 binding sites in the major immediate-early proximal enhancer of human cytomegalovirus have a significant role in viral replication. J. Virol. 79:9597-9607.
26. Isomura, H., T. Tsurumi, and M. F. Stinski. 2004. Role of the proximal enhancer of the major immediate-early promoter in human cytomegalovirus replication. J. Virol. 78:12788-12799.
27. Jault, F. M., J. M. Jault, F. Ruchti, E. A. Fortunato, C. Clark, J. Corbeil, D. D. Richman, and D. H. Spector. 1995. Cytomegalovirus infection induces high levels of cyclins, phosphorylated Rb, and p53, leading to cell cycle arrest. J. Virol. 69:6697-6704.
28. Kalejta, R. F., J. T. Bechtel, and T. Shenk. 2003. Human cytomegalovirus pp71 stimulates cell cycle progression by inducing the proteasome-dependent degradation of the retinoblastoma family of tumor suppressors. Mol. Cell. Biol. 23:1885-1895.
29. Kalejta, R. F., and T. Shenk. 2003. Proteasome-dependent, ubiquitin-independent degradation of the Rb family of tumor suppressors by the human cytomegalovirus pp71 protein. Proc. Natl. Acad. Sci. U. S. A. 100:3263-3268. (Pubitemid 36356571)
30. Kerry, J. A., A. Sehgal, S. W. Barlow, V. J. Cavanaugh, K. Fish, J. A. Nelson, and R. M. Stenberg. 1995. Isolation and characterization of a low-abundance splice variant from the human cytomegalovirus major immediate-early gene region. J. Virol. 69:3868-3872.
31. Korioth, F., G. G. Maul, B. Plachter, T. Stamminger, and J. Frey. 1996. The nuclear domain 10 (ND10) is disrupted by the human cytomegalovirus gene product IE1. Exp. Cell Res. 229:155-158.
32. Lafemina, R. L., M. C. Pizzorno, J. D. Mosca, and G. S. Hayward. 1989. Expression of the acidic nuclear immediate-early protein (IE1) of human cytomegalovirus in stable cell lines and its preferential association with metaphase chromosomes. Virology 172:584-600.
33. Lashmit, P. E., C. A. Lundquist, J. L. Meier, and M. F. Stinski. 2004. Cellular repressor inhibits human cytomegalovirus transcription from the UL127 promoter. J. Virol. 78:5113-5123.
34. Liu, B., T. W. Hermiston, and M. F. Stinski. 1991. A cis-acting element in the major immediate-early (IE) promoter of human cytomegalovirus is required for negative regulation by IE2. J. Virol. 65:897-903.
35. Lu, M., and T. Shenk. 1996. Human cytomegalovirus infection inhibits cell cycle progression at multiple points, including the transition from G1 to S. J. Virol. 70:8850-8857.
36. Lukac, D. M., N. Y. Harel, N. Tanese, and J. C. Alwine. 1997. TAF-like functions of human cytomegalovirus immediate-early proteins. J. Virol. 71:7227-7239.
37. Lukac, D. M., J. R. Manuppello, and J. C. Alwine. 1994. Transcriptional activation by the human cytomegalovirus immediate-early proteins: requirements for simple promoter structures and interactions with multiple components of the transcription complex. J. Virol. 68:5184-5193.
38. Malone, C. L., D. H. Vesole, and M. F. Stinski. 1990. Transactivation of a human cytomegalovirus early promoter by gene products from the immediate- early gene IE2 and augmentation by IE1: mutational analysis of the viral proteins. J. Virol. 64:1498-1506.
39. 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.
40. 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.
41. Mocarski, E. S., T. Shenk, and R. F. Pass. 2007. Cytomegalovirus. In D. M. Knipe and P. M. Howley (ed.), Fields virology. Lippincott Williams & Wilkins, Philadelphia, PA.
42. Murphy, E. A., D. N. Streblow, J. A. Nelson, and M. F. Stinski. 2000. The human cytomegalovirus IE86 protein can block cell cycle progression after inducing transition into the S phase of permissive cells. J. Virol. 74:7108-7118.
43. 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.
44. Nghiem, P., P. K. Park, Y. Kim, C. Vaziri, and S. L. Schreiber. 2001. ATR inhibition selectively sensitizes G1 checkpoint-deficient cells to lethal premature chromatin condensation. Proc. Natl. Acad. Sci. U. S. A. 98:9092-9097.
45. Paulus, C., S. Krauss, and M. Nevels. 2006. A human cytomegalovirus antagonist of type I IFN-dependent signal transducer and activator of transcription signaling. Proc. Natl. Acad. Sci. U. S. A. 103:3840-3845.
46. Petrik, D. T., K. P. Schmitt, and M. F. Stinski. 2007. The autoregulatory and transactivating functions of the human cytomegalovirus IE86 protein use independent mechanisms for promoter binding. J. Virol. 81:5807-5818.
47. 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.
48. Pizzorno, M. C., and G. S. Hayward. 1990. The IE2 gene products of human cytomegalovirus specifically down-regulate expression from the major immediate- early promoter through a target sequence located near the cap site. J. Virol. 64:6154-6165.
49. Poma, E. E., T. F. Kowalik, L. Zhu, J. H. Sinclair, and E. S. Huang. 1996.The human cytomegalovirus IE1-72 protein interacts with the cellular p107 protein and relieves p107-mediated transcriptional repression of an E2Fresponsive promoter. J. Virol. 70:7867-7877.
50. Qian, Z., V. Leung-Pineda, B. Xuan, H. Piwnica-Worms, and D. Yu. 2010. Human cytomegalovirus protein pUL117 targets the mini-chromosome maintenance complex and suppresses cellular DNA synthesis. PLoS Pathog. 6:e1000814.
51. Reinhardt, J., G. B. Smith, C. T. Himmelheber, J. Azizkhan-Clifford, and E. S. Mocarski. 2005. The carboxyl-terminal region of human cyto megalovirusIE1491aa contains an acidic domain that plays a regulatory role and a chromatin-tethering domain that is dispensable during viral replication. J. Virol. 79:225-233.
52. Sanchez, V., C. L. Clark, J. Y. Yen, R. Dwarakanath, and D. H. Spector. 2002. Viable human cytomegalovirus recombinant virus with an internal deletion of the IE2 86 gene affects late stages of viral replication. J. Virol. 76:2973-2989.
53. 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.
54. Sanchez, V., and D. H. Spector. 2006. Cyclin-dependent kinase activity is required for efficient expression and posttranslational modification of human cytomegalovirus proteins and for production of extracellular particles. J. Virol. 80:5886-5896.
55. Sanchez, V., and D. H. Spector. 2008. Subversion of cell cycle regulatory pathways. Curr. Top. Microbiol. Immunol. 325:243-262.
56. 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.
57. Shirakata, M., M. Terauchi, M. Ablikim, K. Imadome, K. Hirai, T. Aso, and Y. Yamanashi. 2002. Novel immediate-early protein IE19 of human cytomegalovirus activates the origin recognition complex I promoter in a cooperative manner with IE72. J. Virol. 76:3158-3167.
58. Shlapobersky, M., R. Sanders, C. Clark, and D. H. Spector. 2006. Repression of HMGA2 gene expression by human cytomegalovirus involves the IE2 86-kilodalton protein and is necessary for efficient viral replication and inhibition of cyclin A transcription. J. Virol. 80:9951-9961.
59. Sommer, M. H., A. L. Scully, and D. H. Spector. 1994. Transactivation by the human cytomegalovirus IE2 86-kilodalton protein requires a dom ain that binds to both the TATA box-binding protein and the retinoblastoma protein. J. Virol. 68:6223-6231.
60. Song, Y. J., and M. F. Stinski. 2002. Effect of the human cytomegalovirusIE86 protein on expression of E2F-responsive genes: a DNA microarray analysis. Proc. Natl. Acad. Sci. U. S. A. 99:2836-2841.
61. Song, Y. J., and M. F. Stinski. 2005. Inhibition of cell division by the human cytomegalovirus IE86 protein: role of the p53 pathway or cyclin-dependent kinase 1/cyclin B1. J. Virol. 79:2597-2603.
62. Stenberg, R. M., D. R. Thomsen, and M. F. Stinski. 1984. Structural analysis of the major immediate early gene of human cytomegalovirus. J. Virol. 49:190-199.
63. 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.
64. Stinski, M. F., and D. T. Petrik. 2008. Functional roles of the human cytomegalovirus essential IE86 protein. Curr. Top. Microbiol. Immunol. 325: 133-152.
65. Stoltzfus, C. M., and J. M. Madsen. 2006. Role of viral splicing elements and cellular RNA binding proteins in regulation of HIV-1 alternative RNA splicing. Curr. HIV Res. 4:43-55.
66. Walker, P. R., and M. Sikorska. 1994. Endonuclease activities, chromatin structure, and DNA degradation in apoptosis. Biochem. Cell Biol. 72:615-623.
67. 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.
68. 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.
69. Wiebusch, L., M. Truss, and C. Hagemeier. 2004. Inhibition of human cytomegalovirus replication by small interfering RNAs. J. Gen. Virol. 85:179-184.
70. Wilkinson, G. W., C. Kelly, J. H. Sinclair, and C. Rickards. 1998. Disruption of PML-associated nuclear bodies mediated by the human cytomegalovirus major immediate early gene product. J. Gen. Virol. 79:1233-1245.
71. Zheng, Z. M. 2004. Regulation of alternative RNA splicing by exon definition and exon sequences in viral and mammalian gene expression. J. Biomed. Sci. 11:278-294.
72. Zhu, H., J. P. Cong, D. Yu, W. A. Bresnahan, and T. E. Shenk. 2002. Inhibition of cyclooxygenase 2 blocks human cytomegalovirus replication. Proc. Natl. Acad. Sci. U. S. A. 99:3932-3937.
73. Zhu, H., Y. Shen, and T. Shenk. 1995. Human cytomegalovirus IE1 and IE2 proteins block apoptosis. J. Virol. 69:7960-7970.
74. Zydek, M., C. Hagemeier, and L. Wiebusch. 2010. Cyclin-dependent kinase activity controls the onset of the HCMV lytic cycle. PLoS Pathog. 6:e1001096.