Osteopontin Facilitates West Nile Virus Neuroinvasion Via Neutrophil "Trojan Horse" Transport
Authors
Affiliations
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.
West Nile virus triggers intestinal dysmotility via T cell-mediated enteric nervous system injury.
Janova H, Zhao F, Desai P, Mack M, Thackray L, Stappenbeck T J Clin Invest. 2024; 134(21).
PMID: 39207863 PMC: 11527448. DOI: 10.1172/JCI181421.
A novel nanocomposite drug delivery system for SARS-CoV-2 infections.
Chintapula U, Karim S, Iyer P, Asokan-Sheeja H, Neupane B, Nazneen F Nanoscale Adv. 2024; 6(15):3747-3758.
PMID: 39050946 PMC: 11265598. DOI: 10.1039/d4na00361f.
Ly6C monocytes in the skin promote systemic alphavirus dissemination.
Holmes A, Lucas C, Brisse M, Ware B, Hickman H, Morrison T Cell Rep. 2024; 43(3):113876.
PMID: 38446669 PMC: 11005330. DOI: 10.1016/j.celrep.2024.113876.
Neurological Manifestations of Perinatal Dengue.
Singh S, Alallah J, Amrit A, Maheshwari A, Boppana S Newborn (Clarksville). 2023; 2(2):158-172.
PMID: 37559696 PMC: 10411360. DOI: 10.5005/jp-journals-11002-0066.
Mechanisms of Neuroinvasion and Neuropathogenesis by Pathologic Flaviviruses.
de Vries L, Harding A Viruses. 2023; 15(2).
PMID: 36851477 PMC: 9965671. DOI: 10.3390/v15020261.