Short hairpin RNA targeting 2B gene of coxsackievirus B3 exhibits potential antiviral effects both in vitro and in vivo

BMC Infect Dis. 2012 Aug 6:12:177. doi: 10.1186/1471-2334-12-177.

Abstract

Background: Coxsackievirus B3 is an important infectious agent of viral myocarditis, pancreatitis and aseptic meningitis, but there are no specific antiviral therapeutic reagents in clinical use. RNA interference-based technology has been developed to prevent the viral infection.

Methods: To evaluate the impact of RNA interference on viral replication, cytopathogenicity and animal survival, short hairpin RNAs targeting the viral 2B region (shRNA-2B) expressed by a recombinant vector (pGCL-2B) or a recombinant lentivirus (Lenti-2B) were tansfected in HeLa cells or transduced in mice infected with CVB3.

Results: ShRNA-2B exhibited a significant effect on inhibition of viral production in HeLa cells. Furthermore, shRNA-2B improved mouse survival rate, reduced the viral tissues titers and attenuated tissue damage compared with those of the shRNA-NC treated control group. Lenti-2B displayed more effective role in inhibition of viral replication than pGCL-2B in vivo.

Conclusions: Coxsackievirus B3 2B is an effective target of gene silencing against coxsackievirus B3 infection, suggesting that shRNA-2B is a potential agent for further development into a treatment for enterviral diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / pharmacology
  • Biological Products / administration & dosage*
  • Biological Products / pharmacology
  • Coxsackievirus Infections / drug therapy*
  • Coxsackievirus Infections / virology
  • Disease Models, Animal
  • Enterovirus B, Human / drug effects*
  • Enterovirus B, Human / genetics
  • HeLa Cells
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / pharmacology
  • Survival Analysis
  • Treatment Outcome
  • Viral Load

Substances

  • Antiviral Agents
  • Biological Products
  • RNA, Small Interfering