Small animal models of filovirus disease: recent advances and future directions

ABSTRACT

Introduction: Small animal models have played a critical role in understanding the pathogenesis and transmission of disease caused by filoviruses. Notably, small animals have served to identify and validate many different approaches to countering infection with these highly pathogenic viruses. Nonetheless, predictive efficacy between each model does not appear to be equivalent as higher order animals seem to be more prognostic and therefore successful in the evaluation of medical countermeasures (MCM).

Areas covered: This review comprehensively details the available small animal models of filovirus infection and discusses the benefits and shortcomings of each model with respect to the development of MCM. An up-to-date evaluation of mouse, hamster, guinea pig, and ferret models is provided.

Expert opinion: The recent development of the domestic ferret model for ebolavirus offers a small animal model that faithfully reproduces most features of human disease without the need for viral adaptation or an immunocompromised host. That being said, choosing a small animal model to evaluate a particular MCM must consider potential confounders associated with each model. These confounding issues include incomplete host immune systems or mutations in the challenge virus that enables the disease.

KEYWORDS:

• Ebola
• Marburg
• filovirus
• therapeutics
• vaccines
• drugs
• animal models
• rodents
• mice
• guinea pigs
• hamsters
• ferrets
• nonhuman primates
• medical countermeasures

Article highlights

• Since the discovery of Marburg virus in 1967, many small animal models have been utilized to investigate the pathogenesis and develop medical countermeasures including vaccines, therapeutics, and diagnostics against filoviruses.

• Human and nonhuman primate pathogenesis is largely in agreement with respect to pathogenic processes; however, many of the available small animal models do not faithfully recapitulate all disease processes observed during filovirus infection.

• Rodent models including mice, hamsters, and guinea pigs require either viral adaptation achieved through serial passage or that the host is immunocompromised to achieve disease reflective of humans or nonhuman primates.

• Refinement of rodent models has allowed for genetic dissection of key signaling pathways important for filovirus pathogenesis.

• Chimeric mouse models supplemented with human cells are being developed to more closely model aspects of human immunology otherwise unattainable in any rodent system.

• The recent development of the domestic ferret model for ebolavirus offers a small animal model that faithfully reproduces most features of human disease without the need for viral adaptation or an immunocompromised host.

• Careful consideration of the strengths and weaknesses of the chosen filovirus model used to evaluate medical countermeasures is vital to ensure the highest level of predictive efficacy prior to evaluation in human clinical trials.

This box summarizes key points contained in the article.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.