Viral nanoparticles associate with regions of inflammation and blood brain barrier disruption during CNS infection.
Targeted treatment of inflammatory diseases of the central nervous system (CNS) remains problematic due to the complex pathogenesis of these disorders and difficulty in drug delivery. The plant virus, cowpea mosaic virus (CPMV), has recently been explored as a nanoparticle delivery system for therapeutics targeting a number of diseases including cancer and neurodegeneration. To understand the biodistribution of CPMV in the CNS, we examined CPMV uptake during infection of mice with neurotropic mouse hepatitis virus (MHV). CPMV localized mainly to the CNS endothelium in areas that contained an intact blood brain barrier. However, in inflammatory lesions containing macrophage/microglial cell infiltration and IgG, CPMV could be detected in the brain parenchyma. Furthermore, CPMV showed rapid internalization in an in vitro model of the BBB. These results suggest that CPMV particles could be used as a vehicle to deliver therapeutics to the damaged CNS during neurodegenerative and infectious diseases of the CNS.
Shriver
Leah P
LP
Department of Cell Biology and Center for Integrative Molecular Biosciences, The Scripps Research Institute, La Jolla, CA 92037, United States.
Koudelka
Kristopher J
KJ
Manchester
Marianne
M
D000818:Animals; D001812:Blood-Brain Barrier / Q000473:pathology / Q000821:virology*; D001921:Brain / Q000473:pathology / Q000821:virology; D002494:Central Nervous System Infections / Q000473:pathology / Q000821:virology*; D017798:Comovirus / Q000502:physiology*; D018352:Coronavirus Infections / Q000503:physiopathology; D016503:Drug Delivery Systems / Q000379:methods; D042783:Endothelial Cells / Q000821:virology; D005260:Female; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D006517:Murine hepatitis virus; D053758:Nanoparticles