title: Comparison of the Pathogenesis of the Angola and Ravn Strains of Marburg Virus in the Outbred Guinea Pig Model.
abstract: BACKGROUND
  Phylogenetic comparisons of known Marburg virus (MARV) strains reveal 2 distinct genetic lineages: Ravn and the Lake Victoria Marburg complex (eg, Musoke, Popp, and Angola strains). Nucleotide variances of >20% between Ravn and other MARV genomes suggest that differing virulence between lineages may accompany this genetic divergence. To date, there exists limited systematic experimental evidence of pathogenic differences between MARV strains.
  
  
  METHODS
  Uniformly lethal outbred guinea pig models of MARV-Angola (MARV-Ang) and MARV-Ravn (MARV-Rav) were developed by serial adaptation. Changes in genomic sequence, weight, temperature, histopathologic findings, immunohistochemical findings, hematologic profiles, circulating biochemical enzyme levels, coagulation parameters, viremia levels, cytokine levels, eicanosoid levels, and nitric oxide production were compared between strains.
  
  
  RESULTS
  MARV-Rav infection resulted in delayed increases in circulating inflammatory and prothrombotic elements, notably lower viremia levels, less severe histologic alterations, and a delay in mean time to death, compared with MARV-Ang infection. Both strains produced more marked coagulation abnormalities than previously seen in MARV-infected mice or inbred guinea pigs.
  
  
  CONCLUSIONS
  Although both strains exhibit great similarity to pathogenic markers of human and nonhuman primate MARV infection, these data highlight several key differences in pathogenicity that may serve to guide the choice of strain and model used for development of vaccines or therapeutics for Marburg hemorrhagic fever.
authors.affiliation: Department of Microbiology and Immunology Galveston National Laboratory, University of Texas Medical Branch at Galveston.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Cross
authors.affiliation: Department of Microbiology and Immunology Galveston National Laboratory, University of Texas Medical Branch at Galveston.
authors.forename: Karla A
authors.initials: KA
authors.lastname: Fenton
authors.affiliation: Department of Microbiology and Immunology Galveston National Laboratory, University of Texas Medical Branch at Galveston.
authors.forename: Joan B
authors.initials: JB
authors.lastname: Geisbert
authors.affiliation: Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ebihara
authors.affiliation: Department of Microbiology and Immunology Galveston National Laboratory, University of Texas Medical Branch at Galveston.
authors.forename: Chad E
authors.initials: CE
authors.lastname: Mire
authors.affiliation: Department of Microbiology and Immunology Galveston National Laboratory, University of Texas Medical Branch at Galveston.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Geisbert
mesh_terms: D000810:Angola; D000818:Animals; D001777:Blood Coagulation / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D006168:Guinea Pigs; D008379:Marburg Virus Disease / Q000378:metabolism / Q000821:virology*; D029024:Marburgvirus / Q000235:genetics / Q000472:pathogenicity*; D009569:Nitric Oxide / Q000378:metabolism; D014766:Viremia / Q000378:metabolism; D014774:Virulence / Q000235:genetics*
chemical_list: D016207:Cytokines; D009569:Nitric Oxide
keywords: Angola; Marburg virus; Ravn; animal model; coagulation; filovirus; guinea pig; pathogenesis