Establishing Potosi Virus as a Human Pathogen

Objectives To establish Potosi virus, a mosquito-borne member of the family Peribunyaviridae , as a neuroinvasive human pathogen. Methods Case report. Results A 37-year-old woman with multiple sclerosis on long-term rituximab developed rapidly progressive dementia. Serial MRI demonstrated progressive generalized atrophy. CSF showed transient, minimal lymphocytic pleocytosis. Extensive infectious, autoimmune, and prion evaluations were unrevealing, but CSF metagenomic sequencing detected all 3 genome segments for Potosi virus. Postmortem examination revealed diffuse meningoencephalitis with T-cell–predominant leptomeningeal and perivascular inflammation. Molecular analyses confirmed multiple nucleotide sequences with >99+% concordance with a known Potosi strain, with widespread viral infection confirmed by immunohistochemistry demonstrating intracellular and extracellular viral antigen. Electron microscopy demonstrated particles of a size consistent with the Peribunyaviridae family. Metagenomic sequencing of RNA extracted from frozen brain tissue identified all 3 Potosi virus gene segments without other infectious entities. Findings were concordant across multiple laboratories and institutions. Discussion Potosi virus can cause fatal neuroinvasive disease in humans, as evidenced by convergent postmortem neuropathologic, molecular, and ultrastructural evidence. Chronic B-cell depletion may increase susceptibility to severe disease with arboviral infections, which may present without conventional CNS inflammatory markers. CSF metagenomic sequencing should be considered in immunocompromised patients with unexplained progressive neurologic decline.