Effective treatment of respiratory alphaherpesvirus infection using RNA interference

Amy Fulton, Sarah T. Peters, Gillian A. Perkins, Keith W. Jarosinski, Armando Damiani, Margaret Brosnahan, Elizabeth L. Buckles, Nikolaus Osterrieder, Gerlinde R. Van de Walle

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Equine herpesvirus type 1 (EHV-1), a member of the Alphaherpesvirinae, is spread via nasal secretions and causes respiratory disease, neurological disorders and abortions. The virus is a significant equine pathogen, but current EHV-1 vaccines are only partially protective and effective metaphylactic and therapeutic agents are not available. Small interfering RNAs (siRNA's), delivered intranasally, could prove a valuable alternative for infection control. siRNA's against two essential EHV-1 genes, encoding the viral helicase (Ori) and glycoprotein B, were evaluated for their potential to decrease EHV-1 infection in a mouse model. Methodology/Principal Fndings: siRNA therapy in vitro significantly reduced virus production and plaque size. Viral titers were reduced 80-fold with 37.5 pmol of a single siRNA or with as little as 6.25 pmol of each siRNA when used in combination. siRNA therapy in vivo significantly reduced viral replication and clinical signs. Intranasal treatment did not require a transport vehicle and proved effective when given up to 12 h before or after infection. Conclusions/Significance: siRNA treatment has potential for both prevention and early treatment of EHV-1 infections.

Original languageEnglish (US)
Article numbere4118
JournalPloS one
Volume4
Issue number1
DOIs
StatePublished - Jan 5 2009
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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