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. 2018 Nov 22;218(suppl_5):S458-S465.
doi: 10.1093/infdis/jiy456.

Distinct Biological Phenotypes of Marburg and Ravn Virus Infection in Macaques

Veronica V Nicholas  1 , Rebecca Rosenke  2 , Friederike Feldmann  2 , Dan Long  2 , Tina Thomas  1 , Dana P Scott  2 , Heinz Feldmann  1 , Andrea Marzi  1
Affiliations

Distinct Biological Phenotypes of Marburg and Ravn Virus Infection in Macaques

Veronica V Nicholas et al. J Infect Dis. .

Abstract

Filoviruses are among the most pathogenic infectious agents known to human, with high destructive potential, as evidenced by the recent Ebola virus epidemic in West Africa. As members of the filovirus family, marburgviruses have caused similar devastating outbreaks, albeit with lower case numbers. In this study we compare the pathogenesis of Ravn virus (RAVV) and Marburg virus (MARV) strains Angola, Musoke, and Ozolin in rhesus and cynomolgus macaques, the 2 nonhuman primate species most commonly used in filovirus research. Our results reveal the most pathogenic MARV strain to be Angola, followed by Musoke, whereas Ozolin is the least pathogenic. We also demonstrate that RAVV is highly pathogenic in cynomolgus macaques but less pathogenic in rhesus macaques. Our results demonstrate a preferential infection of endothelial cells by MARVs; in addition, analysis of tissue samples suggests that lymphocyte and hepatocyte apoptosis might play a role in MARV pathogenicity. This information expands our knowledge about pathogenicity and virulence of marburgviruses.

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Figures

Figure 1.
Figure 1.
Survival and viremia of Marburg virus (MARV)–infected macaques. A, B, Survival curves for rhesus (A) and cynomolgus (B) macaques infected with MARV strain Angola, Musoke, or Ozolin or Ravn virus (RAVV). C, D, Virus titers in the blood of rhesus (C) and cynomolgus (D) macaques infected with MARV Angola, Musoke, or Ozolin or RAVV. Abbreviations: Cyno, cynomolgus; TCID50, median tissue culture infectious dose.
Figure 2.
Figure 2.
Histology, immunohistochemistry, and in situ hybridization of liver samples from a macaque (animal A2) infected with Marburg virus (MARV), strain Angola. A, Hematoxylin-eosin staining shows necrosis (arrow). B, Reticulin silver staining shows reticulin fibers (arrow). C, D, Infected endothelial cells (arrows) demonstrated by immunohistochemistry staining (C) and in situ hybridization (D). All images are 200× original magnification.
Figure 3.
Figure 3.
Histology and immunohistochemistry (IHC) of macaques infected with Marburg virus (MARV), strain Angola, or Ravn virus (RAVV). A, B, Spleen samples from an RAVV-infected rhesus macaque (animal R2), as shown with hematoxylin-eosin (HE) (A) and IHC (B) staining. C, D, Spleen samples from an RAVV-infected cynomolgus macaque (animal R4), as shown with HE (C) (Fi, fibrin; MZH, marginal zone hemorrhage; N, necrosis) and IHC (D) staining. E, F, IHC staining for active caspase 3 in spleen samples from a MARV Angola–infected rhesus macaque (E; animal A2) and an RAVV-infected cynomolgus macaque (F; animal R4). All images are 200× original magnification.
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