title: Comparative pathology of neurovirulent lineage 1 (NY99/385) and lineage 2 (SPU93/01) West Nile virus infections in BALBc mice.
abstract: The pathology in mice infected with neurovirulent South African lineage 2 West Nile virus (WNV) strains has not previously been described. Three- to 4-month-old male BALBc mice were infected with South African neurovirulent lineage 2 (SPU93/01) or lineage 1 (NY385/99) WNV strains and the gross and microscopic central nervous system (CNS) and extra-CNS pathology of both investigated and compared. Mice infected with both lineages showed similar illness, paralysis, and death from days 7 to 11 postinfection (PI). Two survivors of each lineage were euthanized on day 21 PI. WNV infection was confirmed by nested real-time reverse transcription polymerase chain reaction of tissues, mostly brain, in the majority of mice euthanized sick or that died and in 1 healthy lineage 2 survivor. Gross lesions caused by both lineages were identical and included marked gastric and proximal small intestinal fluid distension as described in a previous mouse study, but intestinal microscopic lesions differed. CNS lesions were subtle. Immunohistochemical (IHC)-positive labeling for WNV E protein was found in neurons multifocally in the brain of 3 lineage 1-infected and 3 lineage 2-infected mice from days 9 to 11 PI, 4 of these including brainstem neurons, and of cecal myenteric ganglion neurons in 1 lineage 2-infected day 8 PI mouse. Findings supported hypotheses in hamsters that gastrointestinal lesions are likely of brainstem origin. Ultrastructurally, virus-associated cytoplasmic vesicular or crystalline structures, or amorphous structures, were found to label IHC positive in control-positive avian cardiomyocytes and mouse thalamic neurons, respectively, and WNV-like 50-nm particles, which were scarce, did not label.
authors: Department of Paraclinical Sciences, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, Republic of South Africa Department of Medical Virology, Faculty of Health Sciences, University of Pretoria, Republic of South Africa june.williams@up.ac.za.
authors: J H
authors: JH
authors: Williams
authors: Department of Medical Virology, Faculty of Health Sciences, University of Pretoria, Republic of South Africa.
authors: J D L
authors: JD
authors: Mentoor
authors: Electron Microscopy Unit, Department of Anatomy, Faculty of Veterinary Science, University of Pretoria, Republic of South Africa.
authors: E
authors: E
authors: Van Wilpe
authors: Department of Medical Virology, Faculty of Health Sciences, University of Pretoria, Republic of South Africa Center for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, Sandringham, Johannesburg, Republic of South Africa.
authors: M
authors: M
authors: Venter
mesh_terms: D000818:Animals; D001717:Birds; D001921:Brain / Q000473:pathology; D006224:Cricetinae; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000821:virology; D009474:Neurons / Q000821:virology; D013047:Specific Pathogen-Free Organisms; D014901:West Nile Fever / Q000473:pathology* / Q000662:veterinary*; D014902:West Nile virus / Q000502:physiology* / Q000648:ultrastructure
keywords: BALBc mice; West Nile virus lineages 1 and 2; histopathology; immunohistochemistry; neurovirulent; pathology; ultrastructure