Skip to main content
NCBI home page
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 2007 Mar 20;152(7):1305–1314. doi: 10.1007/s00705-007-0951-z

Silencing E1A mRNA by RNA interference inhibits adenovirus replication

Y-S Chung 1, M-K Kim 1, W-J Lee 1, C Kang 1
PMCID: PMC7087230  PMID: 17597352

Summary

The adenovirus family contains 51 human serotypes, and most human adenoviruses cause widespread respiratory tract infections. Adenovirus infections can result in severe complications in some cases, such as in adenovirus type 11 infection in immunocompromised patients. However, effective treatment methods for adenovirus infections are currently unavailable. This prompted the search for antiviral agents effective against adenovirus infections. In the present study, adenovirus E1A was targeted by RNA interference (RNAi) using synthetic small interfering RNAs (siRNAs) in an attempt to inhibit viral replication, since adenovirus E1A proteins are known to be involved in the transcriptional activation of the viral and cellular genes necessary for controlling the cell cycle and viral replication. The results indicated that the siRNAs effectively reduced the amount of adenovirus E1A mRNA and the levels of replicative intermediates. Additionally, siRNA-mediated gene silencing inhibited adenovirus replication by suppressing the E1A mRNA. These results suggest that the RNAi-mediated targeting of adenovirus E1A may have a potentially therapeutic effect in controlling adenovirus infections.

Keywords: A549 Cell, siRNA Treatment, Human Adenovirus, siRNA Molecule, Plaque Reduction Assay

Footnotes

Yoon-Seok Chung and Min-Kyung Kim contributed equally to this work.

References

  1. Avvakumov N, Sahbegovic M, Zhang Z, Shuen M, Mymryk JS. Analysis of DNA binding by the adenovirus type 5 E1A oncoprotein. J Gen Virol. 2002;83:517–524. doi: 10.1099/0022-1317-83-3-517. [DOI] [PubMed] [Google Scholar]
  2. Capodici J, Kariko K, Weissman D. Inhibition of HIV-1 infection by small interfering RNA-mediated RNA interference. J Immunol. 2002;169:5196–5201. doi: 10.4049/jimmunol.169.9.5196. [DOI] [PubMed] [Google Scholar]
  3. Dagher H, Donninger H, Hutchinson P, Ghildyal R, Bardin P. Rhinovirus detection: comparison of real-time and conventional PCR. J Virol Methods. 2004;117:113–121. doi: 10.1016/j.jviromet.2004.01.003. [DOI] [PubMed] [Google Scholar]
  4. Dykxhoorn DM, Novina CD, Sharp PA. Killing the messenger: short RNAs that silence gene expression. Nature. 2003;4:457–467. doi: 10.1038/nrm1129. [DOI] [PubMed] [Google Scholar]
  5. Ge Q, McManus MT, Nguyen T, Shen CH, Sharp PA, Eisen HN, Chen J. RNA interference of influenza virus production by directly targeting mRNA for degradation and indirectly inhibiting all viral RNA transcription. Proc Natl Acad Sci. 2003;100:2718–2723. doi: 10.1073/pnas.0437841100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hamasaki K, Nakao K, Matsumoto K, Ichikawa T, Ishikawa H, Eguchi K. Short interfering RNA-directed inhibition of hepatitis B virus replication. FEBS Lett. 2003;543:51–54. doi: 10.1016/S0014-5793(03)00400-9. [DOI] [PubMed] [Google Scholar]
  7. Kaneko H, Kato K, Mori S, Shigeta S. Antiviral activity of NMSO3 against adenovirus in vitro. Antiviral Res. 2001;52:281–288. doi: 10.1016/S0166-3542(01)00167-X. [DOI] [PubMed] [Google Scholar]
  8. Kapadia SB, Andersen AB, Chisari FV. Interference of hepatitis C virus RNA replication by short interfering RNAs. Proc Natl Acad Sci. 2003;100:2014–2018. doi: 10.1073/pnas.252783999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kim VN. RNA interference in functional genomics and medicine. J Korean Med Sci. 2003;18:309–318. doi: 10.3346/jkms.2003.18.4.483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kodama E, Shigeta S, Suzuki T, Clercq ED. Application of a gastric cancer cell line (MKN-28) for anti-adenovirus screening using the MTT method. Antiviral Res. 1996;31:159–164. doi: 10.1016/0166-3542(96)06966-5. [DOI] [PubMed] [Google Scholar]
  11. McCown M, Diamond MS, Pekosz A. The utility of siRNA transcripts produced by RNA polymerase I in down regulating viral gene expression and replication of negative- and positive-strand RNA viruses. Virology. 2003;313:514–524. doi: 10.1016/S0042-6822(03)00341-6. [DOI] [PubMed] [Google Scholar]
  12. Mei YF, Skog J, Lindman K, Wadell G. Comparative analysis of the genome organization of human adenovirus 11, a member of the human adenovirus species B, and the commonly used human adenovirus 5 vector, a member of species C. J Gen Virol. 2003;84:2061–2071. doi: 10.1099/vir.0.19178-0. [DOI] [PubMed] [Google Scholar]
  13. Nagl M, Larcher C, Gottardi W. Activity of N-chlorotaurine against herpes simplex- and adenoviruses. Antiviral Res. 1998;38:25–30. doi: 10.1016/S0166-3542(98)00005-9. [DOI] [PubMed] [Google Scholar]
  14. Phipps KM, Martinez A, Lu J, Heinz BA, Zhao G. Small interfering RNA molecules as potential anti-human rhinovirus agents: in vitro potency, specificity, and mechanism. J Antiviral Res. 2004;61:49–55. doi: 10.1016/j.antiviral.2003.08.005. [DOI] [PubMed] [Google Scholar]
  15. Scacheri PC, Rosen OR, Caplen NJ, Wolfsberg TG, Umayam L, Lee JC, Hughes CM, Shanmugam KS, Bhattacharjee A, Meyerson M, Collins FS. Short interfering RNAs can induce unexpected and divergent changes in the levels of untargeted proteins in mammalian cells. Proc Natl Acad Sci. 2004;101:1892–1897. doi: 10.1073/pnas.0308698100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Shen C, Buck AK, Liu X, Winkler M, Reske SN. Gene silencing by adenovirus-delivered siRNA. FEBS Lett. 2003;539:111–114. doi: 10.1016/S0014-5793(03)00209-6. [DOI] [PubMed] [Google Scholar]
  17. Ui-Tei K, Naito Y, Takahashi F, Haraguchi T, Hamazaki HO, Juni A, Ueda R, Saigo K. Guidelines for the selection of highly effective siRNA sequences for mammalian and chick RNA interference. Nucleic Acids Res. 2004;32:936–948. doi: 10.1093/nar/gkh247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Wang G, Berk AJ. In vivo association of adenovirus large E1A protein with the human mediator complex in adenovirus-infected and -transformed cells. J Virol. 2002;76:9186–9193. doi: 10.1128/JVI.76.18.9186-9193.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wiebusch L, Truss M, Hagemeier C. Inhibition of human cytomegalovirus replication by small interfering RNAs. J Gen Virol. 2004;85:179–184. doi: 10.1099/vir.0.19453-0. [DOI] [PubMed] [Google Scholar]
  20. Zhang Y, Li T, Fu L, Yu C, Li Y, Xu X, Wang Y, Ning H, Zhang S, Chen W, Babiuk LA, Chang Z. Silencing SARS-CoV spike protein expression in cultured cells by RNA interference. FEBS Lett. 2004;560:141–146. doi: 10.1016/S0014-5793(04)00087-0. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
  21. Zhao T, Rao XM, Xie X, Li L, Thompson TC, McMasters KM, Zhou HS. Adenovirus with insertion-mutated E1A selectively propagates in liver cancer cells and destroys tumors in vivo. Cancer Res. 2003;63:3073–3078. [PubMed] [Google Scholar]

Articles from Archives of Virology are provided here courtesy of Nature Publishing Group

RESOURCES