title: Epithelial cell lines of the cotton rat (Sigmodon hispidus) are highly susceptible in vitro models to zoonotic Bunya-, Rhabdo-, and Flaviviruses.
abstract: BACKGROUND
  Small mammals such as bats and rodents have been increasingly recognized as reservoirs of novel potentially zoonotic pathogens. However, few in vitro model systems to date allow assessment of zoonotic viruses in a relevant host context. The cotton rat (Sigmodon hispidus) is a New World rodent species that has a long-standing history as an experimental animal model due to its unique susceptibility to human viruses. Furthermore, wild cotton rats are associated with a large variety of known or potentially zoonotic pathogens.
  
  
  METHODS
  A method for the isolation and culture of airway epithelial cell lines recently developed for bats was applied for the generation of rodent airway and renal epithelial cell lines from the cotton rat. Continuous cell lines were characterized for their epithelial properties as well as for their interferon competence. Susceptibility to members of zoonotic Bunya-, Rhabdo-, and Flaviviridae, in particular Rift Valley fever virus (RVFV), vesicular stomatitis virus (VSV), West Nile virus (WNV), and tick-borne encephalitis virus (TBEV) was tested. Furthermore, novel arthropod-derived viruses belonging to the families Bunya-, Rhabdo-, and Mesoniviridae were tested.
  
  
  RESULTS
  We successfully established airway and kidney epithelial cell lines from the cotton rat, and characterized their epithelial properties. Cells were shown to be interferon-competent. Viral infection assays showed high-titre viral replication of RVFV, VSV, WNV, and TBEV, as well as production of infectious virus particles. No viral replication was observed for novel arthropod-derived members of the Bunya-, Rhabdo-, and Mesoniviridae families in these cell lines.
  
  
  CONCLUSIONS
  In the current study, we showed that newly established cell lines from the cotton rat can serve as host-specific in vitro models for viral infection experiments. These cell lines may also serve as novel tools for virus isolation, as well as for the investigation of virus-host interactions in a relevant host species.
authors.affiliation: Institute of Virology, University of Bonn Medical Centre, Sigmund-Freud-Strasse 25, 53127, Bonn, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Ehlen
authors.affiliation: Institute of Virology, University of Bonn Medical Centre, Sigmund-Freud-Strasse 25, 53127, Bonn, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Tödtmann
authors.affiliation: Institute for Medical Microbiology, Immunology & Parasitology (IMMIP), University of Bonn Medical Centre, Sigmund-Freud-Strasse 25, 53127, Bonn, Germany.|Present address: Institute of Laboratory Animal Science, University of Zurich, Zurich, Switzerland.
authors.forename: Sabine
authors.initials: S
authors.lastname: Specht
authors.affiliation: Institute of Virology, University of Bonn Medical Centre, Sigmund-Freud-Strasse 25, 53127, Bonn, Germany.|Present address: Helmholtz Centre for Environmental Research - UFZ, Leipzig, Germany.
authors.forename: René
authors.initials: R
authors.lastname: Kallies
authors.affiliation: Institute of Virology, University of Bonn Medical Centre, Sigmund-Freud-Strasse 25, 53127, Bonn, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Papies
authors.affiliation: Institute of Virology, University of Bonn Medical Centre, Sigmund-Freud-Strasse 25, 53127, Bonn, Germany.
authors.forename: Marcel A
authors.initials: MA
authors.lastname: Müller
authors.affiliation: Institute of Virology, University of Bonn Medical Centre, Sigmund-Freud-Strasse 25, 53127, Bonn, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Junglen
authors.affiliation: Institute of Virology, University of Bonn Medical Centre, Sigmund-Freud-Strasse 25, 53127, Bonn, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Drosten
authors.affiliation: Institute of Virology, University of Bonn Medical Centre, Sigmund-Freud-Strasse 25, 53127, Bonn, Germany. eckerle@virology-bonn.de.
authors.forename: Isabella
authors.initials: I
authors.lastname: Eckerle
mesh_terms: D000818:Animals; D002043:Bunyaviridae / Q000254:growth & development*; D002460:Cell Line; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000821:virology*; D005416:Flavivirus / Q000254:growth & development*; D006801:Humans; D008954:Models, Biological; D012209:Rhabdoviridae / Q000254:growth & development*; D016205:Sigmodontinae; D014776:Virus Cultivation
keywords: Bunyaviruses; Cell culture model; Cotton rat; Emerging viruses; Flaviviruses; Rhabdoviruses; Rodents; Sigmodon hispidus; Zoonotic viruses