Dataset Information

Modeling Ebola Virus Transmission Using Ferrets.

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.

SUBMITTER: de La Vega MA

PROVIDER: S-EPMC6211219 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Modeling Ebola Virus Transmission Using Ferrets.

de La Vega Marc-Antoine MA Soule Geoff G Tran Kaylie N KN Tierney Kevin K He Shihua S Wong Gary G Qiu Xiangguo X Kobinger Gary P GP

mSphere 20181031 5

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 undefine ...[more]

PMID: 30381349

Similar Datasets

Project description:UnlabelledEbola virus (EBOV) transmission is currently poorly characterized and is thought to occur primarily by direct contact with infectious material; however transmission from swine to nonhuman primates via the respiratory tract has been documented. To establish an EBOV transmission model for performing studies with statistical significance, groups of six guinea pigs (gps) were challenged intranasally (i.n.) or intraperitoneally (i.p.) with 10,000 times the 50% lethal dose (LD50) of gp-adapted EBOV, and naive gps were then introduced as cage mates for contact exposure at 1 day postinfection (p.i.). The animals were monitored for survival and clinical signs of disease and quantitated for virus shedding postexposure. Changes in the duration of contact of naive gps with infected animals were evaluated for their impact on transmission efficiency. Transmission was more efficient from i.n.- than from i.p.-challenged gps, with 17% versus 83% of naive gps surviving exposure, respectively. Virus shedding was detected beginning at 3 days p.i. from both i.n.- and i.p.-challenged animals. Contact duration positively correlated with transmission efficiency, and the abrogation of direct contact between infected and naive animals through the erection of a steel mesh was effective at stopping virus spread, provided that infectious animal bedding was absent from the cages. Histopathological and immunohistochemical findings show that i.n.-infected gps display enhanced lung pathology and EBOV antigen in the trachea, which supports increased virus transmission from these animals. The results suggest that i.n.-challenged gps are more infectious to naive animals than their systemically infected counterparts and that transmission occurs through direct contact with infectious materials, including those transported through air movement over short distances.ImportanceEbola is generally thought to be spread between humans though infectious bodily fluids. However, a study has shown that Ebola can be spread from pigs to monkeys without direct contact. Further studies have been hampered, because an economical animal model for Ebola transmission is not available. To address this, we established a transmission model in guinea pigs and determined the mechanisms behind virus spread. The survival data, in addition to microscopic examination of lung and trachea sections, show that mucosal infection of guinea pigs is an efficient model for Ebola transmission. Virus spread is increased with longer contact times with an infected animal and is possible without direct contact between an infected and a naive host but can be stopped if infectious materials are absent. These results warrant consideration for the development of future strategies against Ebola transmission and for a better understanding of the parameters involved in virus spread.

Project description:Avian H7 influenza viruses are recognized as potential pandemic viruses, as personnel often become infected during poultry outbreaks. H7 infections in humans typically cause mild conjunctivitis; however, the H7N9 outbreak in the spring of 2013 has resulted in severe respiratory disease. To date, no H7 viruses have acquired the ability for sustained transmission among humans. Airborne transmission is considered a requirement for the emergence of pandemic influenza, and advanced knowledge of the molecular changes or signature required for transmission would allow early identification of pandemic vaccine seed stocks, screening and stockpiling of antiviral compounds, and eradication efforts focused on flocks harboring threatening viruses. Thus, we sought to determine if a highly pathogenic influenza A H7N1 (A/H7N1) virus with no history of human infection could become capable of airborne transmission among ferrets. We show that after 10 serial passages, A/H7N1 developed the ability to be transmitted to cohoused and airborne contact ferrets. Four amino acid mutations (PB2 T81I, NP V284M, and M1 R95K and Q211K) in the internal genes and a minimal amino acid mutation (K/R313R) in the stalk region of the hemagglutinin protein were associated with airborne transmission. Furthermore, transmission was not associated with loss of virulence. These findings highlight the importance of the internal genes in host adaptation and suggest that natural isolates carrying these mutations be further evaluated. Our results demonstrate that a highly pathogenic avian H7 virus can become capable of airborne transmission in a mammalian host, and they support ongoing surveillance and pandemic H7 vaccine development.The major findings of this report are that a highly pathogenic strain of H7N1 avian influenza virus can be adapted to become capable of airborne transmission in mammals without mutations altering receptor specificity. Changes in receptor specificity have been shown to play a role in the ability of avian influenza viruses to cross the species barrier, and these changes are assumed to be essential. The work reported here challenges this paradigm, at least for the influenza viruses of the H7 subtype, which have recently become the focus of major attention, as they have crossed to humans.

Project description:UnlabelledBundibugyo virus (BDBV) is the etiological agent of a severe hemorrhagic fever in humans with a case-fatality rate ranging from 25 to 36%. Despite having been known to the scientific and medical communities for almost 1 decade, there is a dearth of studies on this pathogen due to the lack of a small animal model. Domestic ferrets are commonly used to study other RNA viruses, including members of the order Mononegavirales To investigate whether ferrets were susceptible to filovirus infections, ferrets were challenged with a clinical isolate of BDBV. Animals became viremic within 4 days and succumbed to infection between 8 and 9 days, and a petechial rash was observed with moribund ferrets. Furthermore, several hallmarks of human filoviral disease were recapitulated in the ferret model, including substantial decreases in lymphocyte and platelet counts and dysregulation of key biochemical markers related to hepatic/renal function, as well as coagulation abnormalities. Virological, histopathological, and immunohistochemical analyses confirmed uncontrolled BDBV replication in the major organs. Ferrets were also infected with Ebola virus (EBOV) to confirm their susceptibility to another filovirus species and to potentially establish a virus transmission model. Similar to what was seen with BDBV, important hallmarks of human filoviral disease were observed in EBOV-infected ferrets. This study demonstrates the potential of this small animal model for studying BDBV and EBOV using wild-type isolates and will accelerate efforts to understand filovirus pathogenesis and transmission as well as the development of specific vaccines and antivirals.ImportanceThe 2013-2016 outbreak of Ebola virus in West Africa has highlighted the threat posed by filoviruses to global public health. Bundibugyo virus (BDBV) is a member of the genus Ebolavirus and has caused outbreaks in the past but is relatively understudied, likely due to the lack of a suitable small animal model. Such a model for BDBV is crucial to evaluating vaccines and therapies and potentially understanding transmission. To address this, we demonstrated that ferrets are susceptible models to BDBV infection as well as to Ebola virus infection and that no virus adaptation is required. Moreover, these animals develop a disease that is similar to that seen in humans and nonhuman primates. We believe that this will improve the ability to study BDBV and provide a platform to test vaccines and therapeutics.

Dataset Information

Modeling Ebola Virus Transmission Using Ferrets.

Publications

Modeling Ebola Virus Transmission Using Ferrets.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets