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: Robert W Cross, Karla A Fenton, Joan B Geisbert, Hideki Ebihara, Chad E Mire, Thomas W Geisbert
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 212 Suppl 2 Pg. S258-70 (Oct 01 2015) ISSN: 1537-6613 [Electronic] United States
• PMID: 26092858 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
• Copyright: Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Chemical References

• Cytokines
• Nitric Oxide

Topics

• Angola
• Animals
• Blood Coagulation (physiology)
• Cytokines (metabolism)
• Female
• Genetic Linkage (genetics)
• Genetic Variation (genetics)
• Guinea Pigs
• Marburg Virus Disease (metabolism, virology)
• Marburgvirus (genetics, pathogenicity)
• Nitric Oxide (metabolism)
• Viremia (metabolism)
• Virulence (genetics)