# Mucosal Taï Forest virus infection causes disease in ferrets

## TL;DR

Researchers developed a ferret model to study TAFV infection via mucosal routes and found that mucosal exposure may offer cross-protection against Ebola virus.

## Contribution

The study introduces a new mucosal ferret model for TAFV and demonstrates cross-protection potential between TAFV and EBOV via mucosal exposure.

## Key findings

- Ferrets infected via intranasal or aerosol routes with TAFV developed mild to severe disease.
- Only ferrets intranasally infected with TAFV and rechallenged with EBOV were protected from disease.
- The study highlights the importance of mucosal exposure in assessing TAFV pathogenicity and cross-protection.

## Abstract

The filovirus Taï Forest virus (TAFV) caused a single human case of infection originating from a chimpanzee outbreak, demonstrating that humans are susceptible to TAFV infection. Existing animal disease models use intramuscular (IM) infection; however, natural filovirus infection likely occurs mucosal. We aimed to develop a ferret disease model by inoculation of TAFV by the IM, intranasal (IN), or aerosol routes. The IM group showed minimal signs of disease while IN and aerosol inoculations resulted in moderate to severe disease and partial lethality. The surviving IN or IM TAFV-infected ferrets were rechallenged IM or IN with Ebola virus (EBOV) as a pilot study assessing the cross-protection potential between these closely related viruses. Only ferrets IN-inoculated with TAFV and IN-inoculated with EBOV were protected from disease, all others succumbed to disease after EBOV infection. This data shows that ferrets are a feasible model to assess TAFV pathogenicity by mucosal exposure routes and that possible cross-protection between TAFV and EBOV may be achieved upon mucosal exposure.

Filoviruses are zoonotic pathogens known to cause outbreaks of hemorrhagic disease in humans. Filovirus human-to-human transmission occurs via bodily fluids likely by exposure of mucosal surfaces. Taï Forest virus (TAFV) is a lesser-known human pathogenic filovirus. There are no well-established small animal disease models for TAFV, specifically no natural TAFV exposure models. We aimed to fill this knowledge gap and developed a small animal disease model using a mucosal route of infection.

Ferrets are an established model of mucosal infection for many viruses, such as influenza, and have been shown to be susceptible to wildtype filovirus infection. Our study demonstrated that only ferrets infected via the intranasal or aerosol routes with TAFV developed mild to severe disease with partial lethality. The intramuscular group survived without developing disease. A subset of the surviving TAFV-infected ferrets was rechallenged in a pilot study with Ebola virus (EBOV) to assess the cross-protection potential between these closely related filoviruses. Interestingly, only ferrets infected intranasally with TAFV and rechallenged intranasally with EBOV survived. This highlights the importance of mucosal exposure to assess TAFV pathogenicity and the cross-protection potential between TAFV and EBOV. Furthermore, this model presents a new opportunity for countermeasure evaluation against TAFV in a small animal.