A phosphorothioate antisense oligodeoxynucleotide specifically inhibits coxsackievirus B3 replication in cardiomyocytes and mouse hearts

Ji Yuan, Paul K.M. Cheung, Huifang Zhang, David Chau, Bobby Yanagawa, Caroline Cheung, Honglin Luo, Yinjing Wang, Agripina Suarez, Bruce M. McManus, Decheng Yang

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Antisense oligodeoxynucleotides (AS-ODNs) are promising therapeutic agents for the treatment of virus-induced diseases. We previously reported that coxsackievirus B3 (CVB3) infectivity could be inhibited effectively in HeLa cells by phosphorothioate AS-ODNs complementary to different regions of the 5′ and 3′ untranslated regions of CVB3 RNA. The most effective target is the proximal terminus of the 3′ untranslated region. To further investigate the potential antiviral role of the AS-ODN targeting this site in cardiomyocytes (HL-1 cell line), corresponding AS-ODN (AS-7) was transfected into the HL-1 cells and followed by CVB3 infection. Analyses by RT-PCR, Western blotting and plaque assay demonstrated that AS-7 strongly inhibits viral RNA and viral protein synthesis as compared to scrambled AS-ODNs. The percent inhibitions of viral RNA transcription and capsid protein VP1 synthesis were 87.6 and 40.1, respectively. Moreover, AS-7 could inhibit ongoing CVB3 infection when it was given after virus infection. The antiviral activity was further evaluated in a CVB3 myocarditis mouse model. Adolescent A/J mice were intravenously administrated with AS-7 or scrambled AS-ODNs prior to and after CVB3 infection. Following a 4-day therapy, the myocardium CVB3 RNA replication decreased by 68% and the viral titers decreased by 0.5 log10 in the AS-7-treated group as compared to the group treated with the scrambled AS-ODNs as determined by RT-PCR, in situ hybridization and viral plaque assay. Taken together, our results demonstrated a great potential for AS-7 to be further developed into an effective treatment towards viral myocarditis as well as other diseases caused by CVB3 infection.

Original languageEnglish (US)
Pages (from-to)703-714
Number of pages12
JournalLaboratory Investigation
Volume84
Issue number6
DOIs
StatePublished - Jun 2004

Keywords

  • Antisense
  • Cardiomyocyte
  • Coxsackievirus B3
  • Mouse
  • Myocarditis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'A phosphorothioate antisense oligodeoxynucleotide specifically inhibits coxsackievirus B3 replication in cardiomyocytes and mouse hearts'. Together they form a unique fingerprint.

  • Cite this

    Yuan, J., Cheung, P. K. M., Zhang, H., Chau, D., Yanagawa, B., Cheung, C., Luo, H., Wang, Y., Suarez, A., McManus, B. M., & Yang, D. (2004). A phosphorothioate antisense oligodeoxynucleotide specifically inhibits coxsackievirus B3 replication in cardiomyocytes and mouse hearts. Laboratory Investigation, 84(6), 703-714. https://doi.org/10.1038/labinvest.3700083