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

Gillian A. Perkins Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.

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Gerlinde R. Van de Walle Department of Comparative Physiology and Biometrics, Faculty of Veterinary Medicine, Ghent University, 9820 Merelbeke, Belgium.

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Nicola Pusterla Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.

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Hollis N. Erb Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.

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Nikolaus Osterrieder Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.

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Abstract

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.

Abstract

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.

Contributor Notes

Dr. Osterrieder's present address is Institut für Virologie, Freie Universität Berlin, 10115 Berlin, Germany.

Presented in poster form at the American College of Veterinary Internal Medicine Forum, Anaheim, Calif, June 2010, and in abstract form at the Third Havemeyer Foundation EHV-1 Workshop, Steamboat Springs, Colo, September 2011.

Supported by the Harry M. Zweig Memorial Fund for Equine Research at Cornell University.

The authors thank Abigail Christman, Lauren Bookbinder, Hillary Wentworth, Meleana Hinchman, Tracy Stokol, Catherine Benson, Laura Goodman, Paula Sharp, Keith Jarosinski, and Benedikt Kaufer for technical assistance.

Address correspondence to Dr. Perkins (gap7@cornell.edu).
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