Title

Chronic Exposure to West Nile Virus Leads to Neuroinvasive-Like Syndrome in Mice (P5.146)

Document Type

Article

Publication Date

4-9-2018

Department

Biological Sciences

Abstract

Objective: The objective was to develop a mouse model of slowly progressing neuroinvasive West Nile virus (WNV) disease that could mimic human condition and help determine the neuropathologic basis of WNV infection.

Background: WNV may cause a significant neuroinvasive disease involving the brain and/or spinal cord. Neuroinvasive WNV infection has a high mortality and many who recover present with long-term deficits, including weakness, fatigue, and cognitive problems. Some of these symptoms are also observed after WNV fever. The exact reasons for lingering symptoms following various clinical presentations of WNV infection remain obscure. This hinders development of specific treatments for neurologic sequelae of WNV infection.

Design/Methods: Seven week old Brainbow-PV Cre mice were treated with a single sub-acute dose (20–50 PFU) of WNV via IP injection (at USM). Mice were kept up to 2, 4 and 6 months post-infection, followed by behavior testing, sacrifice, immunohistochemical and Western blot analyses. Also, cerebellar and spinal cord tissue was processed for total mRNA extraction and gene expression profiling (UMMC’s Molecular and Genomics Facility).

Results: WNV treated mice showed a significant decrease in grip strength at 4 and 6 months post-infection with no balance or motor coordination deficits. The Western blot data revealed unchanged levels of cerebellar neuronal marker proteins at all age intervals; however, astrocytic S100B levels were altered at 2, 4 and 6 months as compared to mock treated animals. The expression profiles of several genes in the cerebellar and spinal cord tissue was significantly altered in WNV treated group; the Toll-like receptor signaling and the cytokine/chemokine signaling were more severely affected in the spinal cord than cerebellum.

Conclusions: Alterations in the expression of astrocyte specific genes, which are members of and/or are related to the above pathways need further analysis, which may reveal new targets or potential biomarkers of WNV infection and assist in developing novel therapies.

Publication Title

Neurology

Volume

90

Issue

15

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