The Forgotten Gate: Choroid Plexus and Blood-CSF Barrier in Arboviral Encephalitis

Mechanisms of arboviral neuroinvasion are still incompletely resolved, despite longstanding emphasis on the blood-brain barrier (BBB) as the principal interface for central nervous system (CNS) entry. While BBB-centered models have been highly informative, they may underrepresent the contribution of other CNS border structures, particularly the choroid plexus and the blood-cerebrospinal fluid barrier (BCSFB). Here, we re-examine the BCSFB as a relevant but unevenly supported neuroinvasion interface in arboviral encephalitis. The strongest direct evidence is currently available for Zika virus (ZIKV), for which experimental studies support infection of choroid plexus-associated cells and CNS access through the blood-CSF axis. Semliki Forest virus (SFV) provides additional direct, although still limited, support for this concept. In contrast, for West Nile virus (WNV), Japanese encephalitis virus (JEV), and tick-borne encephalitis virus (TBEV), evidence for choroid plexus involvement remains indirect or insufficiently resolved, even though neuroinvasion itself is well established. We therefore argue not for replacement of BBB-centered models, but for broader integration of the BCSFB into current frameworks of arboviral CNS invasion. This evidence-based perspective supports a hierarchical, virus-dependent view of choroid plexus involvement and highlights the need for mechanistic studies that directly test when and how this interface contributes to encephalitic disease.