Highly restrictive and directional penetration of the blood cerebral spinal fluid barrier by JCPyV

• DOI: 10.1371/journal.ppat.1012335
• Publication Date: 2024-07-22T17:53:08Z
• Authors: Bethany A. O’Hara; Avraham S. Lukacher; Kaitlin Garabian; Jacob Kaiserman; Evan MacLure; Hiroshi Ishikawa; Horst Schroten; Sheila A. Haley; Walter J. Atwood
• Keywords: Transcytosis; Pinocytosis

The human polyomavirus JCPyV is an opportunistic pathogen that infects greater than 60% of the world's population. virus establishes a persistent and asymptomatic infection in urogenital system but can cause fatal demyelinating disease immunosuppressed or immunomodulated patients following invasion CNS. mechanisms responsible for into CNS tissues are not known direct from blood to cerebral spinal fluid via choroid plexus has been hypothesized. To study potential as site neuroinvasion, we used adult epithelial cell line model blood-cerebrospinal (B-CSF) barrier transwell system. We found these cells formed highly restrictive penetration either free associated with extracellular vesicles (EVJC+). restriction was absolute small amounts EVJC+ penetrated were able establish foci primary astrocytes. Disruption capsaicin did increase leading us hypothesize cell-associated crossed by active process. An inhibitor macropinocytosis increased basolateral (blood side) apical side (CSF side). In contrast, inhibitors clathrin raft dependent transcytosis reduced transport barrier. None drugs inhibited suggesting directionality. Pretreatment cyclosporin A, P-gp, MRP2 BCRP multidrug resistance transporters, restored viral treated inhibitors. Because be susceptible both vitro vivo also examined release infectious preferentially released (CSF) chamber. These data show clearly there two penetration, which capable seeding CSF virus, followed directional virions compartment.