Identification and Pathological Characterization of Persistent Asymptomatic Ebola Virus infection in Rhesus Monkeys

Abstract

Ebola virus (EBOV) persistence in asymptomatic humans and Ebola virus disease (EVD) sequelae have emerged as significant public health concerns since the 20132016 EVD outbreak in Western Africa. Until now, studying how EBOV disseminates into and persists in immune-privileged sites was impossible due to the absence of a suitable animal model. Here, we detect persistent EBOV replication coinciding with systematic inflammatory responses in otherwise asymptomatic rhesus monkeys that had survived infection in the absence of or after treatment with candidate medical countermeasures. We document progressive EBOV dissemination into the eyes, brain and testes through vascular structures, similar to observations in humans. We identify CD68+ cells (macrophages/monocytes) as the cryptic EBOV reservoir cells in the vitreous humour and its immediately adjacent tissue, in the tubular lumina of the epididymides, and in foci of histiocytic inflammation in the brain, but not in organs typically affected during acute infection. In conclusion, our data suggest that persistent EBOV infection in rhesus monkeys could serve as a model for persistent EBOV infection in humans, and we demonstrate that promising candidate medical countermeasures may not completely clear EBOV infection. A rhesus monkey model may lay the foundation to study EVD sequelae and to develop therapies to abolish EBOV persistence.

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Document Details

Document Type
Technical Report
Publication Date
Jul 17, 2017
Accession Number
AD1035786

Entities

People

  • Candace D. Blancett
  • Christopher W. Schellhase
  • Gustavo Palacios
  • Jeffrey W. Froude
  • Jens H. Kuhn
  • Jeremy J. Bearss
  • John M Dye
  • John M. Chance
  • Kathleen A. Cashman
  • Keith A. Koistinen
  • Mei G. Sun
  • Sheli R. Radoshitzky
  • Shelley P Honnold
  • Sina Bavari
  • Travis K. Warren
  • Xiankun Zeng

Organizations

  • National Institutes of Health
  • United States Army Medical Research Institute of Infectious Diseases

Tags

DTIC Thesaurus Topics

  • Blood
  • Blood Vessels
  • Blood-Brain Barrier
  • Brain
  • Cells
  • Central Nervous System
  • Confocal Microscopy
  • Connective Tissue
  • Disease Attributes
  • Ebola Virus
  • Epithelial Cells
  • Equine Encephalitis
  • Eye Diseases
  • Infection
  • Infectious Diseases
  • Laboratory Animals
  • Lymphatic System
  • Neuroglia
  • Peripheral Nervous System
  • Research Facilities
  • Rhesus Monkeys
  • Testis
  • Tissues
  • Uvea
  • Viral Hemorrhagic Fevers
  • Virus Diseases
  • Viruses

Fields of Study

  • Biology

Readers

  • Immunology and Pathology
  • Infectious Disease/Epidemiology
  • Toxicology/Environmental Toxicology