Peripheral Neuronopathy Associated With Ebola Virus Infection in Rhesus Macaques: A Possible Cause of Neurological Signs and Symptoms in Human Ebola Patients

J Infect Dis. 2020 Oct 13;222(10):1745-1755. doi: 10.1093/infdis/jiaa304.

Abstract

Neurological signs and symptoms are the most common complications of Ebola virus disease. However, the mechanisms underlying the neurologic manifestations in Ebola patients are not known. In this study, peripheral ganglia were collected from 12 rhesus macaques that succumbed to Ebola virus (EBOV) disease from 5 to 8 days post exposure. Ganglionitis, characterized by neuronal degeneration, necrosis, and mononuclear leukocyte infiltrates, was observed in the dorsal root, autonomic, and enteric ganglia. By immunohistochemistry, RNAscope in situ hybridization, transmission electron microscopy, and confocal microscopy, we confirmed that CD68+ macrophages are the target cells for EBOV in affected ganglia. Further, we demonstrated that EBOV can induce satellite cell and neuronal apoptosis and microglial activation in infected ganglia. Our results demonstrate that EBOV can infect peripheral ganglia and results in ganglionopathy in rhesus macaques, which may contribute to the neurological signs and symptoms observed in acute and convalescent Ebola virus disease in human patients.

Keywords: Ebola virus; autonomic ganglion; dorsal root ganglion; enteric plexus; parasympathetic nervous system; peripheral nervous system; somatic ganglion; sympathetic nervous system.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Disease Models, Animal
  • Ebolavirus
  • Female
  • Ganglia
  • Ganglia, Spinal / pathology
  • Ganglia, Spinal / virology
  • Ganglion Cysts / pathology
  • Hemorrhagic Fever, Ebola / complications*
  • Hemorrhagic Fever, Ebola / pathology*
  • Hemorrhagic Fever, Ebola / virology
  • Humans
  • Immunohistochemistry
  • Leukocytes, Mononuclear
  • Macaca mulatta
  • Macrophages / pathology
  • Male
  • Microglia / pathology
  • Microglia / virology
  • Necrosis
  • Nerve Degeneration / complications*
  • Nerve Degeneration / pathology*
  • Parasympathetic Nervous System / pathology
  • Peripheral Nervous System Diseases / complications*
  • Peripheral Nervous System Diseases / pathology*
  • Peripheral Nervous System Diseases / virology
  • Sensory Receptor Cells / pathology
  • Sensory Receptor Cells / virology
  • Sympathetic Nervous System / pathology

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human