Volume 24, Number 6—June 2018
Ferrets as Models for Influenza Virus Transmission Studies and Pandemic Risk Assessments
|Parameter||Examples of variability|
|Virus (before ferret introduction)
||Seed stock passage history, stock growth matrix, stock titer, wild-type vs. reverse genetics, plaque-purified vs. quasispecies, storage and propagation conditions
|Ferret (before virus introduction)
||Source/genetic lineage, serostatus, age, sex, weight, neutered or intact status, hormonal treatment (females), anesthetic used, housing conditions
||Inoculation route, method, dose, and volume; buffer for dilution
|Transmission experimental designs||Donor:recipient ratio, number of replicates per containment, caging size and setup, perforation size and exposure area between cages, distance between cages, directional airflow, air changes per hour, temperature and humidity, timing and duration of exposure, frequency and sites for sample collection|
*References for individual studies using these conditions are described in (1).
- Belser JA, Eckert AM, Tumpey TM, Maines TR. Complexities in ferret influenza virus pathogenesis and transmission models. Microbiol Mol Biol Rev. 2016;80:733–44.
- Herfst S, Schrauwen EJ, Linster M, Chutinimitkul S, de Wit E, Munster VJ, et al. Airborne transmission of influenza A/H5N1 virus between ferrets. Science. 2012;336:1534–41.
- Zhu H, Wang D, Kelvin DJ, Li L, Zheng Z, Yoon SW, et al. Infectivity, transmission, and pathology of human-isolated H7N9 influenza virus in ferrets and pigs. Science. 2013;341:183–6.
- Tumpey TM, Maines TR, Van Hoeven N, Glaser L, Solórzano A, Pappas C, et al. A two-amino acid change in the hemagglutinin of the 1918 influenza virus abolishes transmission. Science. 2007;315:655–9.
- Yen HL, Lipatov AS, Ilyushina NA, Govorkova EA, Franks J, Yilmaz N, et al. Inefficient transmission of H5N1 influenza viruses in a ferret contact model. J Virol. 2007;81:6890–8.
- Maines TR, Chen LM, Matsuoka Y, Chen H, Rowe T, Ortin J, et al. Lack of transmission of H5N1 avian-human reassortant influenza viruses in a ferret model. Proc Natl Acad Sci U S A. 2006;103:12121–6.
- Munster VJ, de Wit E, van den Brand JM, Herfst S, Schrauwen EJ, Bestebroer TM, et al. Pathogenesis and transmission of swine-origin 2009 A(H1N1) influenza virus in ferrets. Science. 2009;325:481–3.
- Cox NJ, Trock SC, Burke SA. Pandemic preparedness and the Influenza Risk Assessment Tool (IRAT). Curr Top Microbiol Immunol. 2014;385:119–36.
- World Health Organization. Tool for Influenza Pandemic Risk Assessment (TIPRA). Geneva: The Organization; 2016.
- Imai M, Watanabe T, Hatta M, Das SC, Ozawa M, Shinya K, et al. Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature. 2012;486:420–8.
- Maines TR, Belser JA, Gustin KM, van Hoeven N, Zeng H, Svitek N, et al. Local innate immune responses and influenza virus transmission and virulence in ferrets. J Infect Dis. 2012;205:474–85.
- Oh DY, Lowther S, McCaw JM, Sullivan SG, Leang SK, Haining J, et al. Evaluation of oseltamivir prophylaxis regimens for reducing influenza virus infection, transmission and disease severity in a ferret model of household contact. J Antimicrob Chemother. 2014;69:2458–69.
- Houser KV, Pearce MB, Katz JM, Tumpey TM. Impact of prior seasonal H3N2 influenza vaccination or infection on protection and transmission of emerging variants of influenza A(H3N2)v virus in ferrets. J Virol. 2013;87:13480–9.
- Linster M, van Boheemen S, de Graaf M, Schrauwen EJA, Lexmond P, Mänz B, et al. Identification, characterization, and natural selection of mutations driving airborne transmission of A/H5N1 virus. Cell. 2014;157:329–39.
- Russier M, Yang G, Rehg JE, Wong SS, Mostafa HH, Fabrizio TP, et al. Molecular requirements for a pandemic influenza virus: An acid-stable hemagglutinin protein. Proc Natl Acad Sci U S A. 2016;113:1636–41.
- Yen HL, Liang CH, Wu CY, Forrest HL, Ferguson A, Choy KT, et al. Hemagglutinin-neuraminidase balance confers respiratory-droplet transmissibility of the pandemic H1N1 influenza virus in ferrets. Proc Natl Acad Sci U S A. 2011;108:14264–9.
- Blumenkrantz D, Roberts KL, Shelton H, Lycett S, Barclay WS. The short stalk length of highly pathogenic avian influenza H5N1 virus neuraminidase limits transmission of pandemic H1N1 virus in ferrets. J Virol. 2013;87:10539–51.
- Paules CI, Lakdawala S, McAuliffe JM, Paskel M, Vogel L, Kallewaard NL, et al. The hemagglutinin A stem antibody MEDI8852 prevents and controls disease and limits transmission of pandemic influenza viruses. J Infect Dis. 2017;216:356–65.
- Baz M, Boonnak K, Paskel M, Santos C, Powell T, Townsend A, et al. Nonreplicating influenza A virus vaccines confer broad protection against lethal challenge. MBio. 2015;6:e01487–15.
- Cowling BJ, Lam TT-Y, Yen HL, Poon LLM, Peiris M. Evidence-based options for controlling respiratory virus transmission. [cited 2018 Feb 20]. Emerg Infect Dis. 2017;23.
- Moore IN, Lamirande EW, Paskel M, Donahue D, Kenney H, Qin J, et al. Severity of clinical disease and pathology in ferrets experimentally infected with influenza viruses is influenced by inoculum volume. J Virol. 2014;88:13879–91.
- Gustin KM, Belser JA, Wadford DA, Pearce MB, Katz JM, Tumpey TM, et al. Influenza virus aerosol exposure and analytical system for ferrets. Proc Natl Acad Sci U S A. 2011;108:8432–7.
- Belser JA, Gustin KM, Maines TR, Pantin-Jackwood MJ, Katz JM, Tumpey TM. Influenza virus respiratory infection and transmission following ocular inoculation in ferrets. PLoS Pathog. 2012;8:e1002569.
- Nishiura H, Yen HL, Cowling BJ. Sample size considerations for one-to-one animal transmission studies of the influenza A viruses. PLoS One. 2013;8:e55358.
- Belser JA, Maines TR, Katz JM, Tumpey TM. Considerations regarding appropriate sample size for conducting ferret transmission experiments. Future Microbiol. 2013;8:961–5.
- Frise R, Bradley K, van Doremalen N, Galiano M, Elderfield RA, Stilwell P, et al. Contact transmission of influenza virus between ferrets imposes a looser bottleneck than respiratory droplet transmission allowing propagation of antiviral resistance. Sci Rep. 2016;6:29793.
- Varble A, Albrecht RA, Backes S, Crumiller M, Bouvier NM, Sachs D, et al. Influenza A virus transmission bottlenecks are defined by infection route and recipient host. Cell Host Microbe. 2014;16:691–700.
- Lakdawala SS, Jayaraman A, Halpin RA, Lamirande EW, Shih AR, Stockwell TB, et al. The soft palate is an important site of adaptation for transmissible influenza viruses. Nature. 2015;526:122–5.
- Lakdawala SS, Lamirande EW, Suguitan AL Jr, Wang W, Santos CP, Vogel L, et al. Eurasian-origin gene segments contribute to the transmissibility, aerosol release, and morphology of the 2009 pandemic H1N1 influenza virus. PLoS Pathog. 2011;7:e1002443.
- Gustin KM, Katz JM, Tumpey TM, Maines TR. Comparison of the levels of infectious virus in respirable aerosols exhaled by ferrets infected with influenza viruses exhibiting diverse transmissibility phenotypes. J Virol. 2013;87:7864–73.
- Koster F, Gouveia K, Zhou Y, Lowery K, Russell R, MacInnes H, et al. Exhaled aerosol transmission of pandemic and seasonal H1N1 influenza viruses in the ferret. PLoS One. 2012;7:e33118.
- Lowen AC, Steel J. Roles of humidity and temperature in shaping influenza seasonality. J Virol. 2014;88:7692–5.
- Gustin KM, Belser JA, Veguilla V, Zeng H, Katz JM, Tumpey TM, et al. Environmental conditions affect exhalation of H3N2 seasonal and variant influenza viruses and respiratory droplet transmission in ferrets. PLoS One. 2015;10:e0125874.
- Roberts KL, Shelton H, Stilwell P, Barclay WS. Transmission of a 2009 H1N1 pandemic influenza virus occurs before fever is detected, in the ferret model. PLoS One. 2012;7:e43303.
- Lipsitch M, Barclay W, Raman R, Russell CJ, Belser JA, Cobey S, et al. Viral factors in influenza pandemic risk assessment. eLife. 2016;5:5.
Page created: May 18, 2018
Page updated: May 18, 2018
Page reviewed: May 18, 2018
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.