Predictive Utility of ViroFind Detection of Blood and CSF Virome for Viral Presence in Human Brain Tissue

Viral presence in the brain may contribute to chronic neurologic diseases. However, investigating these associations is limited by the difficulty of directly sampling brain tissue in living individuals. Here, we evaluated whether peripheral viral detection using unbiased target-enrichment next-generation sequencing could inform viral presence in the brain across a diverse set of viral taxa. We applied ViroFind to matched brain, blood (peripheral blood mononuclear cells, spleen, and/or lymph node), and cerebrospinal fluid (CSF) to assess the predictive utility of viral detection in blood and CSF for identifying viral presence in brain samples obtained from the National NeuroAIDS Tissue Consortium, including both HIV-infected (HIV⁺) and HIV-uninfected (HIV^-) individuals without known active viral infection of the brain. Blood negativity was generally more informative for predicting the absence of viruses in the brain than blood positivity for predicting viral presence. CSF viral detection demonstrated limited predictive utility for brain presence across most viral taxa examined. Among blood⁺ individuals, viral burden differed significantly between brain⁺ and brain^- cases for Epstein-Barr virus (EBV), parvovirus, and torque teno virus (TTV). Blood viral burden showed moderate ability to distinguish brain⁺ from brain^- cases for EBV and parvovirus, and strong discriminatory ability for TTV, with similar decision thresholds across HIV⁺ and HIV^- individuals.