1887

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Volume 88, Issue 6

Control of Rta expression critically determines transcription of viral and cellular genes following gammaherpesvirus infection Free

Abstract

The replication and transcriptional activator (Rta), encoded by ORF50 of gammaherpesviruses, initiates the lytic cycle of gene expression; therefore understanding the impact of Rta on viral and cellular gene expression is key to elucidating the transcriptional events governing productive infection and reactivation from latency. To this end, the impact of altering Rta transcription on viral and cellular gene expression was studied in the context of a whole virus infection. Recombinant murine gammaherpesvirus (MHV)-68 engineered to overexpress Rta greatly accelerated expression of specific lytic cycle ORFs, but repressed transcription of the major latency gene, ORF73. Increased expression of Rta accelerated the dysregulation in transcription of specific cellular genes when compared with cells infected with wild-type and revertant viruses. A subset of cellular genes was dysregulated only in cells infected with Rta-overexpressing virus, and never in those infected with non-overexpressing viruses. These data highlight the critical role of Rta abundance in governing viral and cellular gene transcription, and demonstrate the importance of understanding how the relative expression of ORF50 during the virus life cycle impacts on these processes.

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2007-06-01
2024-04-19
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References

  1. Allen M. D., King C., MacDonald T. O., Himes V. 1996; VCAM-1 and E-selectin expression during cytomegalovirus infection in post-transplant myocardial biopsies. Clin Transplant 10:528–537
     [Google Scholar]
  2. Aoki Y., Tosato G. 1999; Role of vascular endothelial growth factor/vascular permeability factor in the pathogenesis of Kaposi's sarcoma-associated herpesvirus-infected primary effusion lymphomas. Blood 94:4247–4254
     [Google Scholar]
  3. Bais C., Santomasso B., Coso O., Arvanitakis L., Raaka E. G., Gutkind J. S., Asch A. S., Cesarman E., Gershengorn M. C., Mesri E. A. 1998; G-protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus is a viral oncogene and angiogenesis activator. Nature 391:86–89 [CrossRef]
     [Google Scholar]
  4. Blackshear P. J. 2002; Tristetraprolin and other CCCH tandem zinc-finger proteins in the regulation of mRNA turnover. Biochem Soc Trans 30:945–952
     [Google Scholar]
  5. Blaskovic D., Stancekova M., Svobodova J., Mistrikova J. 1980; Isolation of five strains of herpesviruses from two species of free living small rodents. Acta Virol 24:468
     [Google Scholar]
  6. Brown H. J., Song M. J., Deng H., Wu T. T., Cheng G., Sun R. 2003; NF- κ B inhibits gammaherpesvirus lytic replication. J Virol 77:8532–8540 [CrossRef]
     [Google Scholar]
  7. Chang H., Gwack Y., Kingston D., Souvlis J., Liang X., Means R. E., Cesarman E., Hutt-Fletcher L., Jung J. U. 2005; Activation of CD21 and CD23 gene expression by Kaposi's sarcoma-associated herpesvirus RTA. J Virol 79:4651–4663 [CrossRef]
     [Google Scholar]
  8. Coleman H. M., Efstathiou S., Stevenson P. G. 2005; Transcription of the murine gammaherpesvirus 68 ORF73 from promoters in the viral terminal repeats. J Gen Virol 86:561–574 [CrossRef]
     [Google Scholar]
  9. Damania B., Jeong J. H., Bowser B. S., DeWire S. M., Staudt M. R., Dittmer D. P. 2004; Comparison of the Rta/Orf50 transactivator proteins of gamma-2-herpesviruses. J Virol 78:5491–5499 [CrossRef]
     [Google Scholar]
  10. Deng H., Young A., Sun R. 2000; Auto-activation of the rta gene of human herpesvirus-8/Kaposi's sarcoma-associated herpesvirus. J Gen Virol 81:3043–3048
     [Google Scholar]
  11. Deng H., Chu J. T., Rettig M. B., Martinez-Maza O., Sun R. 2002; Rta of the human herpesvirus 8/Kaposi sarcoma-associated herpesvirus up-regulates human interleukin-6 gene expression. Blood 100:1919–1921 [CrossRef]
     [Google Scholar]
  12. Eswarakumar V. P., Lax I., Schlessinger J. 2005; Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev 16:139–149 [CrossRef]
     [Google Scholar]
  13. Goodwin D. J., Walters M. S., Smith P. G., Thurau M., Fickenscher H., Whitehouse A. 2001; Herpesvirus saimiri open reading frame 50 (Rta) protein reactivates the lytic replication cycle in a persistently infected A549 cell line. J Virol 75:4008–4013 [CrossRef]
     [Google Scholar]
  14. Gwack Y., Hwang S., Lim C., Won Y. S., Lee C. H., Choe J. 2002; Kaposi's sarcoma-associated herpesvirus open reading frame 50 stimulates the transcriptional activity of STAT3. J Biol Chem 277:6438–6442 [CrossRef]
     [Google Scholar]
  15. Hiscott J., Kwon H., Genin P. 2001; Hostile takeovers: viral appropriation of the NF- κ B pathway. J Clin Invest 107:143–151 [CrossRef]
     [Google Scholar]
  16. Kim Y. C., Bang D., Lee S., Lee K. H. 2000; The effect of herpesvirus infection on the expression of cell adhesion molecules on cultured human dermal microvascular endothelial cells. J Dermatol Sci 24:38–47 [CrossRef]
     [Google Scholar]
  17. Lee J. M., Lee K. H., Weidner M., Osborne B. A., Hayward S. D. 2002; Epstein-Barr virus EBNA2 blocks Nur77-mediated apoptosis. Proc Natl Acad Sci U S A 99:11878–11883 [CrossRef]
     [Google Scholar]
  18. Liu S., Pavlova I. V., Virgin H. W. IV, Speck S. H. 2000; Characterization of gammaherpesvirus 68 gene 50 transcription. J Virol 74:2029–2037 [CrossRef]
     [Google Scholar]
  19. Martinez-Guzman D., Rickabaugh T., Wu T. T., Brown H., Cole S., Song M. J., Tong L., Sun R. 2003; Transcription program of murine gammaherpesvirus 68. J Virol 77:10488–10503 [CrossRef]
     [Google Scholar]
  20. May J. S., Coleman H. M., Smillie B., Efstathiou S., Stevenson P. G. 2004; Forced lytic replication impairs host colonization by a latency-deficient mutant of murine gammaherpesvirus-68. J Gen Virol 85:137–146 [CrossRef]
     [Google Scholar]
  21. McCormick C., Ganem D. 2005; The kaposin B protein of KSHV activates the p38/MK2 pathway and stabilizes cytokine mRNAs. Science 307:739–741 [CrossRef]
     [Google Scholar]
  22. Milner C. M., Day A. J. 2003; TSG-6: a multifunctional protein associated with inflammation. J Cell Sci 116:1863–1873 [CrossRef]
     [Google Scholar]
  23. Murono S., Inoue H., Tanabe T., Joab I., Yoshizaki T., Furukawa M., Pagano J. S. 2001; Induction of cyclooxygenase-2 by Epstein-Barr virus latent membrane protein 1 is involved in vascular endothelial growth factor production in nasopharyngeal carcinoma cells. Proc Natl Acad Sci U S A 98:6905–6910 [CrossRef]
     [Google Scholar]
  24. Nash A. A., Dutia B. M., Stewart J. P., Davison A. J. 2001; Natural history of murine γ -herpesvirus infection. Philos Trans R Soc Lond B Biol Sci 356:569–579 [CrossRef]
     [Google Scholar]
  25. Nicholas J., Coles L. S., Newman C., Honess R. W. 1991; Regulation of the herpesvirus saimiri (HVS) delayed-early 110-kilodalton promoter by HVS immediate-early gene products and a homolog of the Epstein-Barr virus R trans activator. J Virol 65:2457–2466
     [Google Scholar]
  26. Pati S., Cavrois M., Guo H. G., Foulke J. S., Kim J., Jr, Feldman R. A., Reitz M. 2001; Activation of NF- κ B by the human herpesvirus 8 chemokine receptor ORF74: evidence for a paracrine model of Kaposi's sarcoma pathogenesis. J Virol 75:8660–8673 [CrossRef]
     [Google Scholar]
  27. Pavlova I. V., Virgin H. W. IV, Speck S. H. 2003; Disruption of gammaherpesvirus 68 gene 50 demonstrates that Rta is essential for virus replication. J Virol 77:5731–5739 [CrossRef]
     [Google Scholar]
  28. Pavlova I., Lin C. Y., Speck S. H. 2005; Murine gammaherpesvirus 68 Rta-dependent activation of the gene 57 promoter. Virology 333:169–179 [CrossRef]
     [Google Scholar]
  29. Petalidis L., Bhattacharyya S., Morris G. A., Collins V. P., Freeman T. C., Lyons P. A. 2003; Global amplification of mRNA by template-switching PCR: linearity and application to microarray analysis. Nucleic Acids Res 31:e142 [CrossRef]
     [Google Scholar]
  30. Rahbar A., Soderberg-Naucler C. 2005; Human cytomegalovirus infection of endothelial cells triggers platelet adhesion and aggregation. J Virol 79:2211–2220 [CrossRef]
     [Google Scholar]
  31. Reddanna P., Prabhu K. S., Whelan J., Reddy C. C. 2003; Carboxypeptidase A-catalyzed direct conversion of leukotriene C4 to leukotriene F4. Arch Biochem Biophys 413:158–163 [CrossRef]
     [Google Scholar]
  32. Reznik S. E., Fricker L. D. 2001; Carboxypeptidases from A to Z: implications in embryonic development and Wnt binding. Cell Mol Life Sci 58:1790–1804 [CrossRef]
     [Google Scholar]
  33. Rozen S., Skaletsky H. 2000; Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 132:365–386
     [Google Scholar]
  34. Schwarzmann F., Jager M., Prang N., Wolf H. 1998; The control of lytic replication of Epstein-Barr virus in B lymphocytes. Int J Mol Med 1:137–142
     [Google Scholar]
  35. Shahgasempour S., Woodroffe S. B., Garnett H. M. 1997; Alterations in the expression of ELAM-1, ICAM-1 and VCAM-1 after in vitro infection of endothelial cells with a clinical isolate of human cytomegalovirus. Microbiol Immunol 41:121–129 [CrossRef]
     [Google Scholar]
  36. Speck S. H., Chatila T., Flemington E. 1997; Reactivation of Epstein-Barr virus: regulation and function of the BZLF1 gene. Trends Microbiol 5:399–405 [CrossRef]
     [Google Scholar]
  37. Springer T. A. 1995; Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration. Annu Rev Physiol 57:827–872 [CrossRef]
     [Google Scholar]
  38. Stevenson P. G., Boname J. M., de Lima B., Efstathiou S. 2002; A battle for survival: immune control and immune evasion in murine γ -herpesvirus-68 infection. Microbes Infect 4:1177–1182 [CrossRef]
     [Google Scholar]
  39. Sun R., Lin S. F., Gradoville L., Yuan Y., Zhu F., Miller G. 1998; A viral gene that activates lytic cycle expression of Kaposi's sarcoma-associated herpesvirus. Proc Natl Acad Sci U S A 95:10866–10871 [CrossRef]
     [Google Scholar]
  40. Vendrell J., Querol E., Aviles F. X. 2000; Metallocarboxypeptidases and their protein inhibitors. Structure, function and biomedical properties. Biochim Biophys Acta 1477284–298 [CrossRef]
     [Google Scholar]
  41. West J. T., Wood C. 2003; The role of Kaposi's sarcoma-associated herpesvirus/human herpesvirus-8 regulator of transcription activation (RTA) in control of gene expression. Oncogene 22:5150–5163 [CrossRef]
     [Google Scholar]
  42. Whitehouse A., Cooper M., Hall K. T., Meredith D. M. 1998; The open reading frame (ORF) 50a gene product regulates ORF 57 gene expression in herpesvirus saimiri. J Virol 72:1967–1973
     [Google Scholar]
  43. Wu T. T., Usherwood E. J., Stewart J. P., Nash A. A., Sun R. 2000; Rta of murine gammaherpesvirus 68 reactivates the complete lytic cycle from latency. J Virol 74:3659–3667 [CrossRef]
     [Google Scholar]
  44. Wu T. T., Tong L., Rickabaugh T., Speck S., Sun R. 2001; Function of Rta is essential for lytic replication of murine gammaherpesvirus 68. J Virol 75:9262–9273 [CrossRef]
     [Google Scholar]
  45. Zhu J., Trang P., Kim K., Zhou T., Deng H., Liu F. 2004; Effective inhibition of Rta expression and lytic replication of Kaposi's sarcoma-associated herpesvirus by human RNase P. Proc Natl Acad Sci U S A 101:9073–9078 [CrossRef]
     [Google Scholar]
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Control of Rta expression critically determines transcription of viral and cellular genes following gammaherpesvirus infection
J. Gen. Virol. 88, 1689 (2007); https://doi.org/10.1099/vir.0.82548-0
/content/journal/jgv/10.1099/vir.0.82548-0
/content/journal/jgv/10.1099/vir.0.82548-0
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