Abstract

Filoviruses are zoonotic, negative-sense RNA viruses, most of which are capable of causing severe disease in humans and nonhuman primates, often with high case fatality rates. Among these viruses, those belonging to the Ebolavirus genus—particularly Ebola virus, Sudan virus, and Bundibugyo virus—represent some of the most pathogenic to humans. Taï Forest virus (TAFV) is thought to be among the least pathogenic ebolaviruses; however, only a single non-fatal case has been documented in humans, in 1994. With the recent success of the ferret as a lethal model for a number of ebolaviruses, we set out to evaluate its suitability as a model for TAFV. Our results demonstrate that, unlike other ebolaviruses, TAFV infection in ferrets does not result in lethal disease. None of the intramuscularly inoculated animals demonstrated any overt signs of disease, whereas the intranasally inoculated animals exhibited mild to moderate weight loss during the early stage of infection but recovered quickly. Low levels of viral RNA were detected in the blood and tissues of several animals, particularly the intranasally inoculated animals, and all animals mounted a humoral immune response, with high titers of GP-specific IgG detectable as early as 14 days post-infection. These data provide additional insight into the pathogenesis of TAFV.

Highlights

  • Filoviruses are zoonotic, negative-sense, single-stranded RNA viruses belonging to the family Filoviridae of the order Mononegavirales

  • Plasma samples collected on −1, 14, 20, and 26 dpi were subjected to an enzymelinked immunosorbent assay (ELISA) developed in-house to quantify Taï Forest virus (TAFV) GP-specific immunoglobulin G (IgG)

  • The ferret is highly susceptible to lethal infection with evaluating ebolavirus pathogenesis

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Summary

Introduction

Filoviruses are zoonotic, negative-sense, single-stranded RNA viruses belonging to the family Filoviridae of the order Mononegavirales These viruses are the causative agent of Filovirus Disease (FVD), a form of viral hemorrhagic fever affecting both humans and nonhuman primates (NHPs), often with high case fatality rates [1,2]. TAFV infections have previously been evaluated in NHPs (Macaca fascicularis), immunodeficient mice (IFN-α/βR−/− ), and Egyptian fruit bats (Rousettus Aegypticus) [15], there still remains no well-characterized animal model for studying TAFV pathogenesis This is likely due to the fact that TAFV has yet to cause any significant outbreaks, and by extension can be regarded as a low public health risk and a low research priority. Having an animal model for TAFV would prove useful for the evaluation of cross-reactive or pan-filovirus therapeutics and vaccines

Ethics Statement
Viruses
Animals
Plasma Biochemistry and Complete Blood Counts
Quantification of Viral RNA by RT-qPCR
Generation and Purification of TAFV GP
Evaluation of Humoral Immune Response by ELISA
Data Analysis
Ferrets
Transient Viremia Early after Infection
No Major Perturbations in Hematology or Complete Blood Counts
High Titers of TAFV GP-Specific IgG Detectable as Early as 14 dpi
Discussion
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