LAUSR

Effective therapeutics have been developed against acute Ebola virus disease (EVD) in both humans and experimentally infected nonhuman primates. However, the risk of viral persistence and associated disease recrudescence in survivors receiving these therapeutics remains unclear. In contrast to rhesus macaques that survived Ebola virus (EBOV) exposure in the absence of treatment, we discovered that EBOV, despite being cleared from all other organs, persisted in the brain ventricular system of rhesus macaque survivors that had received monoclonal antibody (mAb) treatment. In mAb-treated macaque survivors, EBOV persisted in macrophages infiltrating the brain ventricular system, including the choroid plexuses. This macrophage infiltration was accompanied by severe tissue damage, including ventriculitis, choroid plexitis, and meningoencephalitis. Specifically, choroid plexus endothelium-derived EBOV infection led to viral persistence in the macaque brain ventricular system. This resulted in apoptosis of ependymal cells, which constitute the blood–cerebrospinal fluid barrier of the choroid plexuses. Fatal brain-confined recrudescence of EBOV infection manifested as severe inflammation, local pathology, and widespread infection of the ventricular system and adjacent neuropil in some of the mAb-treated macaque survivors. This study highlights organ-specific EBOV persistence and fatal recrudescent disease in rhesus macaque survivors after therapeutic treatment and has implications for the long-term follow-up of human survivors of EVD. Description Ebola virus persists in the brain ventricular system of nonhuman primates treated with monoclonal antibodies. Ebola virus: Hiding in plain sight The host-pathogen determinants of Ebola virus (EBOV) persistence and disease recrudescence in immune-privileged organs, including any association with standard-of-care monoclonal antibody–based treatments, remain to be elucidated. In new work, Liu et al. report frequent EBOV persistence in the brain ventricular system of nonhuman primates that survived acute disease after monoclonal antibody–based treatment. Viral persistence was associated with lethal recrudescence of disease including severe inflammation in the brain. These findings have implications for long-term follow-up efforts to reduce the individual (disease relapse/recrudescence) and public health (reignition of outbreaks) consequences of viral persistence in survivors of EBOV infection.