Osteopontin Facilitates West Nile Virus Neuroinvasion via Neutrophil “Trojan Horse” Transport

Authors

Amber M. Paul, University of Southern MississippiFollow
Dhiraj Acharya, University of Southern Mississippi
Laurel Duty, University of Southern Mississippi
E. Ashley Thompson, University of Southern Mississippi
Linda Le, University of Southern Mississippi
Dobrivoje S. Stokic, Methodist Rehabilitation Center
A. Arturo Leis, Methodist Rehabilitation Center, Mayo Clinic
Fengwei Bai, University of Southern Mississippi

Submitting Campus

Daytona Beach

Department

Human Factors and Behavioral Neurobiology

Document Type

Article

Publication/Presentation Date

7-5-2017

Abstract/Description

West Nile virus (WNV) can cause severe human neurological diseases including encephalitis and meningitis. The mechanisms by which WNV enters the central nervous system (CNS) and host factors that are involved in WNV neuroinvasion are not completely understood. The proinflammatory chemokine osteopontin (OPN) is induced in multiple neuroinflammatory diseases and is responsible for leukocyte recruitment to sites of its expression. In this study, we found that WNV infection induced OPN expression in both human and mouse cells. Interestingly, WNV-infected OPN deficient (Opn−/−) mice exhibited a higher survival rate (70%) than wild type (WT) control mice (30%), suggesting OPN plays a deleterious role in WNV infection. Despite comparable levels of viral load in circulating blood cells and peripheral organs in the two groups, WNV-infected polymorphonuclear neutrophil (PMN) infiltration and viral burden in brain of Opn−/− mice were significantly lower than in WT mice. Importantly, intracerebral administration of recombinant OPN into the brains of Opn−/− mice resulted in increased WNV-infected PMN infiltration and viral burden in the brain, which was coupled to increased mortality. The overall results suggest that OPN facilitates WNV neuroinvasion by recruiting WNV-infected PMNs into the brain.

Publication Title

Scientific Reports

DOI

https://doi.org10.1038/s41598-017-04839-7

Publisher

Nature Publishing Group

Additional Information

Dr. Paul was not affiliated with Embry-Riddle Aeronautical University at the time this paper was published.

Scholarly Commons Citation

Paul, A. M., Acharya, D., Duty, L., Thompson, E., Le, L., Stokic, D. S., Leis, A., & Bai, F. (2017). Osteopontin Facilitates West Nile Virus Neuroinvasion via Neutrophil “Trojan Horse” Transport. Scientific Reports, 7(). https://doi.org10.1038/s41598-017-04839-7