Comparison of the Pathogenesis of the Angola and Ravn Strains of Marburg Virus in the Outbred Guinea Pig Model

Robert Cross, Karla A. Fenton, Joan B. Geisbert, Hideki Ebihara, Chad Mire, Thomas Geisbert

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)S258-S270
JournalJournal of Infectious Diseases
Volume212
DOIs
StatePublished - Oct 1 2015

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Marburgvirus
Angola
Guinea Pigs
Virus Diseases
Viremia
Virulence
Marburg Virus Disease
Victoria
Lakes
Primates

Keywords

  • Angola
  • animal model
  • coagulation
  • filovirus
  • Guinea pig
  • Marburg virus
  • pathogenesis
  • Ravn

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Comparison of the Pathogenesis of the Angola and Ravn Strains of Marburg Virus in the Outbred Guinea Pig Model. / Cross, Robert; Fenton, Karla A.; Geisbert, Joan B.; Ebihara, Hideki; Mire, Chad; Geisbert, Thomas.

In: Journal of Infectious Diseases, Vol. 212, 01.10.2015, p. S258-S270.

Research output: Contribution to journalArticle

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