1887

Abstract

Small interfering RNAs (siRNAs) are the mediators of a sequence-specific process of gene silencing called RNA interference (RNAi). Here, we show that synthetic siRNAs against essential gene products of human cytomegalovirus (HCMV) can trigger RNAi in serum-starved, infected primary fibroblasts, as well as in U373 cells, leading to effective inhibition of viral DNA replication. This opens new possibilities for antiviral strategies and for the analysis of viral and cellular genes important to HCMV physiology.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.19453-0
2004-01-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/85/1/vir850179.html?itemId=/content/journal/jgv/10.1099/vir.0.19453-0&mimeType=html&fmt=ahah

References

  1. Azad R. F., Driver V. B., Tanaka K., Crooke R. M., Anderson K. P. 1993; Antiviral activity of a phosphorothioate oligonucleotide complementary to RNA of the human cytomegalovirus major immediate-early region. Antimicrob Agents Chemother 37:1945–1954
    [Google Scholar]
  2. Biswas N., Sanchez V., Spector D. H. 2003; Human cytomegalovirus infection leads to accumulation of geminin and inhibition of the licensing of cellular DNA replication. J Virol 77:2369–2376
    [Google Scholar]
  3. Bresnahan W. A., Boldogh I., Thompson E. A., Albrecht T. 1996; Human cytomegalovirus inhibits cellular DNA synthesis and arrests productively infected cells in late G1. Virology 224:150–160
    [Google Scholar]
  4. Caplen N. J., Parrish S., Imani F., Fire A., Morgan R. A. 2001; Specific inhibition of gene expression by small double-stranded RNAs in invertebrate and vertebrate systems. Proc Natl Acad Sci U S A 98:9742–9747
    [Google Scholar]
  5. Capodici J., Kariko K., Weissman D. 2002; Inhibition of HIV-1 infection by small interfering RNA-mediated RNA interference. J Immunol 169:5196–5201
    [Google Scholar]
  6. Coburn G. A., Cullen B. R. 2002; Potent and specific inhibition of human immunodeficiency virus type 1 replication by RNA interference. J Virol 76:9225–9231
    [Google Scholar]
  7. Elbashir S. M., Harborth J., Lendeckel W., Yalcin A., Weber K., Tuschl T. 2001; Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411:494–498
    [Google Scholar]
  8. Elbashir S. M., Harborth J., Weber K., Tuschl T. 2002; Analysis of gene function in somatic mammalian cells using small interfering RNAs. Methods 26:199–213
    [Google Scholar]
  9. Fire A., Xu S., Montgomery M. K., Kostas S. A., Driver S. E., Mello C. C. 1998; Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans . Nature 391:806–811
    [Google Scholar]
  10. Ge Q., McManus M. T., Nguyen T., Shen C. H., Sharp P. A., Eisen H. N., Chen J. 2003; RNA interference of influenza virus production by directly targeting mRNA for degradation and indirectly inhibiting all viral RNA transcription. Proc Natl Acad Sci U S A 100:2718–2723
    [Google Scholar]
  11. Gitlin L., Karelsky S., Andino R. 2002; Short interfering RNA confers intracellular antiviral immunity in human cells. Nature 418:430–434
    [Google Scholar]
  12. Hamilton A. J., Baulcombe D. C. 1999; A species of small antisense RNA in posttranscriptional gene silencing in plants. Science 286:950–952
    [Google Scholar]
  13. Hannon G. J. 2002; RNA interference. Nature 418:244–251
    [Google Scholar]
  14. Heider J. A., Bresnahan W. A., Shenk T. E. 2002; Construction of a rationally designed human cytomegalovirus variant encoding a temperature-sensitive immediate-early 2 protein. Proc Natl Acad Sci U S A 99:3141–3146
    [Google Scholar]
  15. Jacque J. M., Triques K., Stevenson M. 2002; Modulation of HIV-1 replication by RNA interference. Nature 418:435–438
    [Google Scholar]
  16. Kapadia S. B., Brideau-Andersen A., Chisari F. V. 2003; Interference of hepatitis C virus RNA replication by short interfering RNAs. Proc Natl Acad Sci U S A 100:2014–2018
    [Google Scholar]
  17. Lu M., Shenk T. 1996; Human cytomegalovirus infection inhibits cell cycle progression at multiple points, including the transition from G1 to S. J Virol 70:8850–8857
    [Google Scholar]
  18. McManus M. T., Sharp P. A. 2002; Gene silencing in mammals by small interfering RNAs. Nat Rev Genet 3:737–747
    [Google Scholar]
  19. Martinez M. A., Gutierrez A., Armand-Ugon M., Blanco J., Parera M., Gomez J., Clotet B., Este J. A. 2002; Suppression of chemokine receptor expression by RNA interference allows for inhibition of HIV-1 replication. AIDS 16:2385–2390
    [Google Scholar]
  20. Noris E., Zannetti C., Demurtas A., Sinclair J., De Andrea M., Gariglio M., Landolfo S. 2002; Cell cycle arrest by human cytomegalovirus 86-kDa IE2 protein resembles premature senescence. J Virol 76:12135–12148
    [Google Scholar]
  21. Randall G., Grakoui A., Rice C. M. 2003; Clearance of replicating hepatitis C virus replicon RNAs in cell culture by small interfering RNAs. Proc Natl Acad Sci U S A 100:235–240
    [Google Scholar]
  22. Salvant B. S., Fortunato E. A., Spector D. H. 1998; Cell cycle dysregulation by human cytomegalovirus: influence of the cell cycle phase at the time of infection and effects on cyclin transcription. J Virol 72:3729–3741
    [Google Scholar]
  23. Surabhi R. M., Gaynor R. B. 2002; RNA interference directed against viral and cellular targets inhibits human immunodeficiency virus type 1 replication. J Virol 76:12963–12973
    [Google Scholar]
  24. Wiebusch L., Hagemeier C. 1999; Human cytomegalovirus 86-kilodalton IE2 protein blocks cell cycle progression in G1. J Virol 73:9274–9283
    [Google Scholar]
  25. Wiebusch L., Uecker R., Hagemeier C. 2003; Human cytomegalovirus prevents replication licensing by inhibiting MCM loading onto chromatin. EMBO Rep 4:42–46
    [Google Scholar]
  26. Wilson J. A., Jayasena S., Khvorova A. 7 other authors 2003; RNA interference blocks gene expression and RNA synthesis from hepatitis C replicons propagated in human liver cells. Proc Natl Acad Sci U S A 100:2783–2788
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.19453-0
Loading
/content/journal/jgv/10.1099/vir.0.19453-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error