title: Immune Response to Marburg Virus Angola Infection in Nonhuman Primates.
abstract: BACKGROUND
  The 2005 outbreak of Marburg virus (MARV) infection in Angola was the most lethal MARV infection outbreak in history, with a case-fatality rate (90%) similar to that for Zaire ebolavirus (EBOV) infection. However, very little is known about the pathogenicity of MARV Angola, as few studies have been conducted to date. Therefore, the immune response was examined in MARV Angola-infected nonhuman primates.
  
  
  METHODS
  Cynomolgus macaques were infected with MARV Angola and monitored for survival. The effect of MARV Angola on the immune system was examined by immunophenotyping whole-blood and by analyzing cytokine and chemokine levels in plasma and spleen specimens, using flow cytometry.
  
  
  RESULTS
  The prominent clinical findings were rapid onset of disease and death (mean time after infection, 6.7 days), fever, depression, anorexia, petechial rash, and lymphopenia. Specifically, T, B, and natural killer cells were severely depleted in the blood by day 6. The typical cytokine storm was present, with levels of interferon γ, tumor necrosis factor, interleukin 6, and CCL2 rising in the blood early during infection.
  
  
  CONCLUSIONS
  MARV Angola displayed the same virulence and disease pathology as EBOV. MARV Angola appears to cause a more rapid onset and severe outcome of infection than other MARV strains.
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada.
authors.forename: Lisa
authors.initials: L
authors.lastname: Fernando
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada Department of Medical Microbiology.
authors.forename: Xiangguo
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada.
authors.forename: P Leno
authors.initials: PL
authors.lastname: Melito
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada Department of Immunology, University of Manitoba, Winnipeg, Canada.
authors.forename: Kinola J N
authors.initials: KJ
authors.lastname: Williams
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada.
authors.forename: Friederike
authors.initials: F
authors.lastname: Feldmann
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada Department of Medical Microbiology.
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Jones
authors.affiliation: Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada.
authors.forename: Judie B
authors.initials: JB
authors.lastname: Alimonti
mesh_terms: D000810:Angola; D000818:Animals; D018932:Chemokine CCL2 / Q000276:immunology; D004195:Disease Models, Animal; D029043:Ebolavirus / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology / Q000821:virology; D008251:Macaca / Q000276:immunology / Q000821:virology; D008379:Marburg Virus Disease / Q000276:immunology* / Q000821:virology; D029024:Marburgvirus / Q000276:immunology*; D011323:Primates / Q000276:immunology* / Q000821:virology; D013154:Spleen / Q000276:immunology / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014774:Virulence / Q000276:immunology
chemical_list: D018932:Chemokine CCL2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: Ebolavirus; Filovirus; Marburg Angola; Marburgvirus; cynomolgus macaques; cytokines; lymphocytes; natural killer cells; nonhuman primates