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.

Oral Antibiotic Treatment of Mice Exacerbates the Disease Severity of Multiple Flavivirus Infections

“…Since previous reports have documented WNV infection in the gut ( Brown et al, 2007 ; Kimura et al, 2010 ; Williams et al, 2015 ), we examined viral burden along the length of the gastrointestinal tract. We observed more WNV at days 8–10 after infection in the duodenum, ileum, and colon of VNAM-treated mice compared to vehicle-treated controls ( Figure 2C ).…”

West Nile Virus spread and differential chemokine response in the central nervous system of mice: Role in pathogenic mechanisms of encephalitis

“…These findings may suggest the existence of different response patterns to infection and inflammatory damage/milieu depending on the neuronal location. In that sense, WNV neuronal‐specific tropism and inflammatory changes have been observed between different phylogenetic strains within the same WNV lineage, between WNV lineage 1 and 2 (Donadieu et al, ; Williams, Mentoor, Wilpe, & Venter, ), differences also described between different neurotropic viruses, such lyssavirus (Chai, She, Huang, & Fu, ; Hicks et al, ).…”

Comparative Pathology of West Nile Virus in Humans and Non-Human Animals

“…Thymic atrophy has been described in affected mice, and similarly, the thymus has been affected in ducklings and other birds [154,162]. Gastrointestinal lesions in mice including dilation of the stomach and small intestine and villus blunting (shortening) have been seen in association with degeneration and necrosis of intestinal myenteric ganglia [155,163]. This may serve as a model for gastrointestinal dysmotility seen in humans after flavivirus infection [164].…”