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Ebola virus persistence and disease recrudescence in the brains of antibody-treated nonhuman primate survivors.
Liu, Jun; Trefry, John C; Babka, April M; Schellhase, Christopher W; Coffin, Kayla M; Williams, Janice A; Raymond, Jo Lynne W; Facemire, Paul R; Chance, Taylor B; Davis, Neil M; Scruggs, Jennifer L; Rossi, Franco D; Haddow, Andrew D; Zelko, Justine M; Bixler, Sandra L; Crozier, Ian; Iversen, Patrick L; Pitt, Margaret L; Kuhn, Jens H; Palacios, Gustavo; Zeng, Xiankun.
Afiliação
  • Liu J; United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA.
  • Trefry JC; United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA.
  • Babka AM; United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA.
  • Schellhase CW; United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA.
  • Coffin KM; United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA.
  • Williams JA; United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA.
  • Raymond JLW; United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA.
  • Facemire PR; United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA.
  • Chance TB; United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA.
  • Davis NM; United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA.
  • Scruggs JL; United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA.
  • Rossi FD; United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA.
  • Haddow AD; United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA.
  • Zelko JM; United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA.
  • Bixler SL; United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA.
  • Crozier I; Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
  • Iversen PL; United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA.
  • Pitt ML; United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA.
  • Kuhn JH; Integrated Research Facility at Fort Detrick (IRF-Frederick), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Frederick, MD 21702, USA.
  • Palacios G; United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA.
  • Zeng X; United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA.
Sci Transl Med ; 14(631): eabi5229, 2022 02 09.
Article em En | MEDLINE | ID: mdl-35138912
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article