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Journal of Virology, June 2005, p. 7528-7534, Vol. 79, No. 12
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.12.7528-7534.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Invasion of the Central Nervous System in a Porcine Host by Nipah Virus

Hana Weingartl,1,2* Stefanie Czub,1 John Copps,1 Yohannes Berhane,1 Deborah Middleton,3 Peter Marszal,1 Jason Gren,1 Greg Smith,1 Shelley Ganske,1 Lisa Manning,1 and Markus Czub2,4

National Centre for Foreign Animal Disease, Canadian Food Inspection Agency, Canadian Science Centre for Human and Animal Health, Winnipeg, Canada,1 Australian Animal Health Laboratory, CSIRO, Geelong, Australia,3 National Microbiology Laboratory, Public Health Agency of Canada, Canadian Science Centre for Human and Animal Health, Winnipeg, Canada,4 Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada2

Received 23 November 2004/ Accepted 1 March 2005

Nipah virus, a newly emerged zoonotic paramyxovirus, infects a number of species. Human infections were linked to direct contact with pigs, specifically with their body fluids. Clinical signs in human cases indicated primarily involvement of the central nervous system, while in pigs the respiratory system was considered the primary virus target, with only rare involvement of the central nervous system. Eleven 5-week-old piglets were infected intranasally, orally, and ocularly with 2.5 x 105 PFU of Nipah virus per animal and euthanized between 3 and 8 days postinoculation. Nipah virus caused neurological signs in two out of eleven inoculated pigs. The rest of the pigs remained clinically healthy. Virus was detected in the respiratory system (turbinates, nasopharynx, trachea, bronchus, and lung in titers up to 105.3 PFU/g) and in the lymphoreticular system (endothelial cells of blood and lymphatic vessels, submandibular and bronchiolar lymph nodes, tonsil, and spleen with titers up to 106 PFU/g). Virus presence was confirmed in the nervous system of both sick and apparently healthy animals (cranial nerves, trigeminal ganglion, brain, and cerebrospinal fluid, with titers up to 107.7 PFU/g of tissue). Nipah virus distribution was confirmed by immunohistochemistry. The study presents novel findings indicating that Nipah virus invaded the central nervous system of the porcine host via cranial nerves as well as by crossing the blood-brain barrier after initial virus replication in the upper respiratory tract.

* Corresponding author. Mailing address: National Centre for Foreign Animal Disease, Canadian Food Inspection Agency, Canadian Science Centre for Human and Animal Health, 1015 Arlington St., Winnipeg, MB R3E 3M4, Canada. Phone: (204) 789-2027. Fax: (204) 789-2027. E. mail: hweingartl{at}inspection.gc.ca.

Journal of Virology, June 2005, p. 7528-7534, Vol. 79, No. 12
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.12.7528-7534.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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