Effective treatment of respiratory alphaherpesvirus infection using RNA interference.
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
siRNA treatment has potential for both prevention and early treatment of EHV-1 infections.
Fulton
Amy
A
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
Peters
Sarah T
ST
Perkins
Gillian A
GA
Jarosinski
Keith W
KW
Damiani
Armando
A
Brosnahan
Margaret
M
Buckles
Elizabeth L
EL
Osterrieder
Nikolaus
N
Van de Walle
Gerlinde R
GR
D000281:Administration, Intranasal; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D004268:DNA-Binding Proteins / Q000235:genetics; D004195:Disease Models, Animal; D006566:Herpesviridae Infections / Q000628:therapy / Q000662:veterinary*; D004861:Herpesvirus 1, Equid / Q000235:genetics*; D006734:Horse Diseases / Q000628:therapy* / Q000821:virology; D006736:Horses; D007249:Inflammation / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D034622:RNA Interference / Q000276:immunology*; D034741:RNA, Small Interfering / Q000627:therapeutic use*; D012141:Respiratory Tract Infections / Q000628:therapy / Q000662:veterinary* / Q000821:virology; D014759:Viral Envelope Proteins / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics; D014779:Virus Replication
D000893:Anti-Inflammatory Agents; D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C040495:glycoprotein B, Simplexvirus; C055789:origin-binding proteins, viral