Evaluation of metaphylactic RNA interference to prevent equine herpesvirus type 1 infection in experimental herpesvirus myeloencephalopathy in horses.

OBJECTIVE To evaluate metaphylactic RNA interference to prevent equine herpesvirus type 1 (EHV-1) infection in experimental herpesvirus myeloencephalopathy in horses and to determine whether horses infected with a neuropathogenic strain of the virus that develop equine herpesvirus myeloencephalopathy (EHM) have differences in viremia. ANIMALS 13 seronegative horses. PROCEDURES EHV-1 strain Ab4 was administered intranasally on day 0, and small interfering RNAs (siRNAs [EHV-1 specific siRNAs {n = 7} or an irrelevant siRNA {6}]) were administered intranasally 24 hours before and 12, 24, 36, and 48 hours after infection. Physical and neurologic examinations, nasal swab specimens, and blood samples were collected for virus isolation and quantitative PCR assay. Data from the study were combined with data from a previous study of 14 horses. RESULTS No significant difference was detected in clinical variables, viremia, or detection of EHV-1 in nasal swab specimens of horses treated with the EHV-1 targeted siRNAs (sigB3-siOri2) versus controls. No significant differences in viremia were detected between horses that developed EHM and those that did not. CONCLUSIONS AND CLINICAL RELEVANCE Administration of siRNAs targeted against EHV-1 around the time of EHV-1 infection was not protective with this experimental design. Horses infected with the neuropathogenic EHV-1 strain Ab4 that developed EHM did not have a more pronounced viremia.

[1]  G. R. Van de Walle,et al.  Equine alphaherpesviruses (EHV-1 and EHV-4) differ in their efficiency to infect mononuclear cells during early steps of infection in nasal mucosal explants. , 2011, Veterinary microbiology.

[2]  A. Quintana,et al.  Immunological characterization of the equine airway epithelium and of a primary equine airway epithelial cell culture model. , 2011, Veterinary immunology and immunopathology.

[3]  Young Jik Kwon,et al.  Efficient and targeted delivery of siRNA in vivo , 2010, The FEBS journal.

[4]  E. Hodžić,et al.  Use of quantitative real-time PCR for the detection of Salmonella spp. in fecal samples from horses at a veterinary teaching hospital. , 2010, Veterinary journal.

[5]  P. Rottier,et al.  Experimental infection with neuropathogenic equid herpesvirus type 1 (EHV-1) in adult horses. , 2010, Veterinary journal.

[6]  L. Duchateau,et al.  Replication kinetics of neurovirulent versus non-neurovirulent equine herpesvirus type 1 strains in equine nasal mucosal explants. , 2010, The Journal of general virology.

[7]  S. Hussey,et al.  Control of EHV-1 viremia and nasal shedding by commercial vaccines. , 2010, Vaccine.

[8]  Rob Lambkin-Williams,et al.  A randomized, double-blind, placebo-controlled study of an RNAi-based therapy directed against respiratory syncytial virus , 2010, Proceedings of the National Academy of Sciences.

[9]  H. Erb,et al.  The effect of siRNA treatment on experimental equine herpesvirus type 1 (EHV-1) infection in horses , 2009, Virus Research.

[10]  G. R. Van de Walle,et al.  A single-nucleotide polymorphism in a herpesvirus DNA polymerase is sufficient to cause lethal neurological disease. , 2009, The Journal of infectious diseases.

[11]  K. Osterrieder,et al.  Equine herpesvirus-1 consensus statement. , 2009, Journal of veterinary internal medicine.

[12]  Nikolaus Osterrieder,et al.  Effective Treatment of Respiratory Alphaherpesvirus Infection Using RNA Interference , 2009, PloS one.

[13]  G. Allen Risk factors for development of neurologic disease after experimental exposure to equine herpesvirus-1 in horses. , 2008, American journal of veterinary research.

[14]  R. S. Erkert,et al.  Pharmacokinetics of valacyclovir in the adult horse. , 2008, Journal of veterinary pharmacology and therapeutics.

[15]  C. Carter,et al.  Prevalence of latent, neuropathogenic equine herpesvirus-1 in the Thoroughbred broodmare population of central Kentucky. , 2008, Equine veterinary journal.

[16]  G. Palù,et al.  A Point Mutation in a Herpesvirus Polymerase Determines Neuropathogenicity , 2007, PLoS pathogens.

[17]  H. Nauwynck,et al.  Pharmacokinetics of Acyclovir after Intravenous Infusion of Acyclovir and after Oral Administration of Acyclovir and Its Prodrug Valacyclovir in Healthy Adult Horses , 2007, Antimicrobial Agents and Chemotherapy.

[18]  H. Nauwynck,et al.  In vitro susceptibility of six isolates of equine herpesvirus 1 to acyclovir, ganciclovir, cidofovir, adefovir, PMEDAP and foscarnet. , 2007, Veterinary microbiology.

[19]  G. Allen,et al.  Outbreak of neurologic disease caused by equine herpesvirus-1 at a university equestrian center. , 2007, Journal of veterinary internal medicine.

[20]  G. Allen,et al.  Quantification by real-time PCR of the magnitude and duration of leucocyte-associated viraemia in horses infected with neuropathogenic vs. non-neuropathogenic strains of EHV-1. , 2010, Equine veterinary journal.

[21]  W. D. Wilson,et al.  Cytokine gene signatures in neural tissue of horses with equine protozoal myeloencephalitis or equine herpes type 1 myeloencephalopathy , 2006, Veterinary Record.

[22]  J. Kydd,et al.  The equine immune response to equine herpesvirus-1: the virus and its vaccines. , 2006, Veterinary immunology and immunopathology.

[23]  C. Clarke,et al.  Pharmacokinetics of acyclovir after single intravenous and oral administration to adult horses. , 2006, Journal of veterinary internal medicine.

[24]  C. van Maanen,et al.  Equine herpesvirus type 1-associated myeloencephalopathy in The Netherlands: a four-year retrospective study (1999-2003). , 2006, Journal of veterinary internal medicine.

[25]  N. Osterrieder,et al.  Comparison of the efficacy of inactivated combination and modified-live virus vaccines against challenge infection with neuropathogenic equine herpesvirus type 1 (EHV-1). , 2006, Vaccine.

[26]  R. Bowden,et al.  Analysis of Equid Herpesvirus 1 Strain Variation Reveals a Point Mutation of the DNA Polymerase Strongly Associated with Neuropathogenic versus Nonneuropathogenic Disease Outbreaks , 2006, Journal of Virology.

[27]  N. Zhong,et al.  Using siRNA in prophylactic and therapeutic regimens against SARS coronavirus in Rhesus macaque , 2005, Nature Medicine.

[28]  S. Barik,et al.  Inhibition of respiratory viruses by nasally administered siRNA , 2005, Nature Medicine.

[29]  N. Edington,et al.  The role of endothelial cell infection in the endometrium, placenta and foetus of equid herpesvirus 1 (EHV-1) abortions. , 1991, Journal of comparative pathology.

[30]  G. Dickinson,et al.  An outbreak of paresis in mares and geldings associated with equid herpesvirus 1 , 1981, Veterinary Record.