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. 2018 Oct 31;3(5):e00309-18.
doi: 10.1128/mSphere.00309-18.

Modeling Ebola Virus Transmission Using Ferrets

Affiliations

Modeling Ebola Virus Transmission Using Ferrets

Marc-Antoine de La Vega et al. mSphere. .

Abstract

Ebola virus (EBOV) has been responsible for sporadic outbreaks in Central Africa since 1976 and has the potential of causing social disruption and public panic as illustrated by the 2013-2016 epidemic in West Africa. Transmission of EBOV has been described to occur via contact with infected bodily fluids, supported by data indicating that infectious EBOV could be cultured from blood, semen, saliva, urine, and breast milk. Parameters influencing transmission of EBOV are, however, largely undefined in part due to the lack of an established animal model to study mechanisms of pathogen spread. Here, we investigated EBOV transmissibility in male and female ferrets. After intranasal challenge, an infected animal was placed in direct contact with a naive ferret and in contact with another naive ferret (separated from the infected animal by a metal mesh) that served as the indirect-contact animal. All challenged animals, male direct contacts, and one male indirect contact developed disease and died. The remaining animals were not viremic and remained asymptomatic but developed EBOV-glycoprotein IgM and/or IgG specific antibodies-indicative of virus transmission. EBOV transmission via indirect contact was frequently observed in this model but resulted in less-severe disease compared to direct contact. Interestingly, these observations are consistent with the detection of specific antibodies in humans living in areas of EBOV endemicity.IMPORTANCE Our knowledge regarding transmission of EBOV between individuals is vague and is mostly limited to spreading via direct contact with infectious bodily fluids. Studying transmission parameters such as dose and route of infection is nearly impossible in naturally acquired cases-hence the requirement for a laboratory animal model. Here, we show as a proof of concept that ferrets can be used to study EBOV transmission. We also show that transmission in the absence of direct contact is frequent, as all animals with indirect contact with the infected ferrets had detectable antibodies to the virus, and one succumbed to infection. Our report provides a new small-animal model for studying EBOV transmission that does not require adaptation of the virus, providing insight into virus transmission among humans during epidemics.

Keywords: Ebola virus; animal models; ferret; filovirus; transmission.

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Figures

FIG 1
FIG 1
Experimental setting of the transmission study. Challenged animals were placed on the outer half of the divided units along with a nonchallenged, direct-contact animal. Indirect-contact animals were placed in the inner half of the units. Directional airflow is illustrated by arrows, where clean air was introduced in the caging system from the outer half of the unit, passed through each cage, and evacuated through the middle section of the system. Challenged animals are represented by red biohazard symbols, while black biohazard symbols represent nonchallenged animals. Male ferrets were located on the left, and female ferrets were on the right.
FIG 2
FIG 2
Survival and clinical parameters of challenged and contact ferrets. Clinical parameters of male and female ferrets challenged or not with EBOV-Makona-C05 are presented. (a) Survival. (b) Temperature. (c) Clinical score. (d) Body weight percent change. Key: C, challenged animal; D, direct-contact animal; I, indirect-contact animal; M, male (left column); F, female (right column); *, animal was found dead and could not be scored.
FIG 3
FIG 3
Viral loads and shedding from all animals. Viral loads are measured by RT-qPCR in the blood of male and female ferrets (a), oral swabs (b), nasal washes (c), and rectal swabs (d). Key: C, challenged animal; D, direct-contact animal; I, indirect-contact animal; M, male (left column); F, female (right column). Note that a blood sample was not available from animal IM3 on day 19 as it was found dead.
FIG 4
FIG 4
Humoral response of challenged and contact ferrets. Data represent endpoint titers of IgM (a and b) and IgG (c and d) antibodies against the glycoprotein of EBOV in the serum of challenged and contact ferrets at euthanasia. C, challenged animal; D, direct-contact animal; I, indirect-contact animal; M, male (left column); F, female (right column).

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