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Review
. 2016:2016:8059607.
doi: 10.1155/2016/8059607. Epub 2016 Feb 18.

Adapted Lethality: What We Can Learn from Guinea Pig-Adapted Ebola Virus Infection Model

S V Cheresiz  1 , E A Semenova  1 , A A Chepurnov  2
Affiliations
Review

Adapted Lethality: What We Can Learn from Guinea Pig-Adapted Ebola Virus Infection Model

S V Cheresiz et al. Adv Virol. 2016.

Abstract

Establishment of small animal models of Ebola virus (EBOV) infection is important both for the study of genetic determinants involved in the complex pathology of EBOV disease and for the preliminary screening of antivirals, production of therapeutic heterologic immunoglobulins, and experimental vaccine development. Since the wild-type EBOV is avirulent in rodents, the adaptation series of passages in these animals are required for the virulence/lethality to emerge in these models. Here, we provide an overview of our several adaptation series in guinea pigs, which resulted in the establishment of guinea pig-adapted EBOV (GPA-EBOV) variants different in their characteristics, while uniformly lethal for the infected animals, and compare the virologic, genetic, pathomorphologic, and immunologic findings with those obtained in the adaptation experiments of the other research groups.

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Figures

Figure 1
Figure 1
Adaptation series of wild-type Mayinga strain EBOV to guinea pigs and mice resulting in the establishment of 8mc, K-5, GLA, and GPA-P7 lethal guinea pig-adapted virus variants and a paradoxical high-titer, avirulent mouse-adapted virus variant D-5.
Figure 2
Figure 2
Wild-type EBOV nonlethal infection in guinea pigs. Electron microscopy of the liver.
Figure 3
Figure 3
GPA-EBOV lethal infection in guinea pigs. Electron microscopy of the liver.
Figure 4
Figure 4
Complement activity in the intact and prevaccinated guinea pigs infected with lethal GPA-EBOV-8mc strain or nonlethal wild-type EBOV Mayinga strain. Animals infected with nonlethal influenza virus A/Aichi/2/68 (H3N2) strain, intact animals, and guinea pigs vaccinated with inactivated nonlethal Mayinga strain EBOV while not infected were used as different controls of complement activity. Slow lagging dynamics of complement activity in guinea pigs infected with nonlethal Mayinga strain EBOV is contrasting to the rapid onset/drop peak of complement activity in the intact and prevaccinated animals infected with a lethal 8mc strain GPA-EBOV.
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