Reoma LB, Trindade CJ, Monaco MC, et al. - Researchers describe the first case of fatal JC virus (JCV) encephalopathy following immunosuppressive treatment that included ruxolitinib. Incorporating next generation sequencing, Sanger sequencing, tissue immunohistochemistry, and formalin-fixed hemisphere 7T magnetic resonance imaging, postmortem analysis was carried out. A new 12bp insertion that changed the transcription site binding pattern in an otherwise “wild-type virus,” which has long been presumed to be the nonpathogenic form of JCV, was revealed by JCV DNA isolated from postmortem tissue samples. The presence of infection in cortical neurons, hippocampal neurons, and glial and endothelial cells was shown by anti-VP1 staining. The findings of this case extend the spectrum of recognized JCV diseases related to broad-spectrum immunosuppression, including JAK-STAT inhibitors, as well as provide information about an additional neurotropic virus strain of the archetype variety.