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

33 Citations (Scopus)

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 1 2004

Fingerprint

Enterovirus
Oligodeoxyribonucleotides
Cardiac Myocytes
Coxsackievirus Infections
Myocarditis
Viral RNA
3' Untranslated Regions
Virus Diseases
Viral Plaque Assay
Antiviral Agents
RNA
Polymerase Chain Reaction
5' Untranslated Regions
Capsid Proteins
Viral Proteins
Therapeutics
HeLa Cells
In Situ Hybridization
Myocardium
Western Blotting

Keywords

  • Antisense
  • Cardiomyocyte
  • Coxsackievirus B3
  • Mouse
  • Myocarditis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

A phosphorothioate antisense oligodeoxynucleotide specifically inhibits coxsackievirus B3 replication in cardiomyocytes and mouse hearts. / Yuan, Ji; Cheung, Paul K.M.; Zhang, Huifang; Chau, David; Yanagawa, Bobby; Cheung, Caroline; Luo, Honglin; Wang, Yinjing; Suarez, Agripina; McManus, Bruce M.; Yang, Decheng.

In: Laboratory Investigation, Vol. 84, No. 6, 01.06.2004, p. 703-714.

Research output: Contribution to journalArticle

Yuan, J, Cheung, PKM, Zhang, H, Chau, D, Yanagawa, B, Cheung, C, Luo, H, Wang, Y, Suarez, A, McManus, BM & Yang, D 2004, 'A phosphorothioate antisense oligodeoxynucleotide specifically inhibits coxsackievirus B3 replication in cardiomyocytes and mouse hearts', Laboratory Investigation, vol. 84, no. 6, pp. 703-714. https://doi.org/10.1038/labinvest.3700083
Yuan, Ji ; Cheung, Paul K.M. ; Zhang, Huifang ; Chau, David ; Yanagawa, Bobby ; Cheung, Caroline ; Luo, Honglin ; Wang, Yinjing ; Suarez, Agripina ; McManus, Bruce M. ; Yang, Decheng. / A phosphorothioate antisense oligodeoxynucleotide specifically inhibits coxsackievirus B3 replication in cardiomyocytes and mouse hearts. In: Laboratory Investigation. 2004 ; Vol. 84, No. 6. pp. 703-714.
@article{c7e964c1d60c49009e38d988e71f6fe0,
title = "A phosphorothioate antisense oligodeoxynucleotide specifically inhibits coxsackievirus B3 replication in cardiomyocytes and mouse hearts",
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.",
keywords = "Antisense, Cardiomyocyte, Coxsackievirus B3, Mouse, Myocarditis",
author = "Ji Yuan and Cheung, {Paul K.M.} and Huifang Zhang and David Chau and Bobby Yanagawa and Caroline Cheung and Honglin Luo and Yinjing Wang and Agripina Suarez and McManus, {Bruce M.} and Decheng Yang",
year = "2004",
month = "6",
day = "1",
doi = "10.1038/labinvest.3700083",
language = "English (US)",
volume = "84",
pages = "703--714",
journal = "Laboratory Investigation",
issn = "0023-6837",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - A phosphorothioate antisense oligodeoxynucleotide specifically inhibits coxsackievirus B3 replication in cardiomyocytes and mouse hearts

AU - Yuan, Ji

AU - Cheung, Paul K.M.

AU - Zhang, Huifang

AU - Chau, David

AU - Yanagawa, Bobby

AU - Cheung, Caroline

AU - Luo, Honglin

AU - Wang, Yinjing

AU - Suarez, Agripina

AU - McManus, Bruce M.

AU - Yang, Decheng

PY - 2004/6/1

Y1 - 2004/6/1

N2 - 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.

AB - 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.

KW - Antisense

KW - Cardiomyocyte

KW - Coxsackievirus B3

KW - Mouse

KW - Myocarditis

UR - http://www.scopus.com/inward/record.url?scp=2642574290&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2642574290&partnerID=8YFLogxK

U2 - 10.1038/labinvest.3700083

DO - 10.1038/labinvest.3700083

M3 - Article

C2 - 15094712

AN - SCOPUS:2642574290

VL - 84

SP - 703

EP - 714

JO - Laboratory Investigation

JF - Laboratory Investigation

SN - 0023-6837

IS - 6

ER -