TY - JOUR
T1 - Effective treatment of respiratory alphaherpesvirus infection using RNA interference
AU - Fulton, Amy
AU - Peters, Sarah T.
AU - Perkins, Gillian A.
AU - Jarosinski, Keith W.
AU - Damiani, Armando
AU - Brosnahan, Margaret
AU - Buckles, Elizabeth L.
AU - Osterrieder, Nikolaus
AU - Van de Walle, Gerlinde R.
PY - 2009/1/5
Y1 - 2009/1/5
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0004118
DO - 10.1371/journal.pone.0004118
M3 - Article
C2 - 19122813
AN - SCOPUS:58149463225
SN - 1932-6203
VL - 4
JO - PloS one
JF - PloS one
IS - 1
M1 - e4118
ER -