An antiviral small-interfering RNA simultaneously effective against the most prevalent enteroviruses causing acute hemorrhagic conjunctivitis

Invest Ophthalmol Vis Sci. 2011 Jan 5;52(1):58-63. doi: 10.1167/iovs.09-5051.

Abstract

Purpose: Acute hemorrhagic conjunctivitis (AHC), a highly contagious eye disease, is caused primarily by either enterovirus 70 (EV70) or coxsackievirus A24 (CVA24) infection. Yet methods to prevent or cure AHC are not available. Recent evidence has shown that small-interfering RNAs (siRNAs), mediators of posttranscriptional gene knockdown, can act as effective antiviral agents. Thus, the authors attempted to develop a novel siRNA-based anti-AHC agent effective against both EV70 and CVA24.

Methods: Concurrent screening of the entire viral genome sequences of EV70 and CVA24 using the CAPSID program identified five different siRNA candidates complementary to genome regions of both viruses. The antiviral potentials of these siRNAs were assessed by treating MRC5 and primary human conjunctival cells with the siRNAs and following this with viral challenge.

Results: Among the five siRNAs, AHCe-3D-3 siRNA showed excellent cytoprotective effects and dramatic decreases in virus replication and virus protein synthesis. This siRNA, targeting the virus polymerase 3D gene, also induced similar antiviral effects in primary human conjunctival cells.

Conclusions: These findings strongly suggest that the AHCe-3D-3 siRNA, homologous to two different AHC-associated enteroviruses, can provide equivalent antiviral activities against both AHC-causing enteroviruses. Such an siRNA may be developed as a clinically valuable AHC control agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents
  • Blotting, Western
  • Conjunctiva / cytology
  • Conjunctivitis, Acute Hemorrhagic / genetics
  • Conjunctivitis, Acute Hemorrhagic / therapy*
  • Conjunctivitis, Acute Hemorrhagic / virology
  • Coxsackievirus Infections / genetics
  • Coxsackievirus Infections / therapy*
  • Coxsackievirus Infections / virology
  • Enterovirus C, Human / physiology*
  • Enterovirus D, Human / physiology*
  • Enterovirus Infections / genetics
  • Enterovirus Infections / therapy*
  • Enterovirus Infections / virology
  • Fibroblasts / virology
  • Fluorescent Antibody Technique, Indirect
  • Genome, Viral
  • HeLa Cells / virology
  • Humans
  • RNA Interference / physiology
  • RNA, Small Interfering / genetics*
  • Viral Structural Proteins / metabolism
  • Virus Replication / physiology*

Substances

  • Antiviral Agents
  • RNA, Small Interfering
  • Viral Structural Proteins