Meningeal lymphatic vessels mediate neurotropic viral drainage from the central nervous system

Abstract

Recent studies have demonstrated that brain meningeal lymphatic vessels (MLVs) act as a drainage path directly into the cervical lymph nodes (CLNs) for macromolecules contained in the cerebrospinal fluid (CSF). However, the role of MLVs during CNS viral infection remains unexplored. Here, we found that infection with several neurotropic viruses in mice promotes MLV expansion but also causes impaired MLV-mediated drainage of macromolecules. Notably, MLVs could drain virus from the CNS to CLNs. Surgical ligation of the lymph vessels or photodynamic ablation of dorsal MLVs increased neurological damage and mortality of virus-infected mice. By contrast, pretreatment with vascular endothelial growth factor C promoted expansion of functional MLVs and alleviated the effects of viral infection. Together, these data indicate that functional MLVs facilitate virus clearance, and MLVs represent a critical path for virus spreading from the CNS to the CLNs. MLV-based therapeutic strategies may thus be useful for alleviating infection-induced neurological damage. This study finds that during acute viral infection of the CNS, meningeal lymphatic vessels (MLVs) can transport virus from the CNS to draining cervical lymph nodes. VEGF-C-induced expansion of functional MLVs facilitated virus clearance.