Epithelial cell lines of the cotton rat (Sigmodon hispidus) are highly susceptible in vitro models to zoonotic Bunya-, Rhabdo-, and Flaviviruses.

Lukas Ehlen,Isabella Eckerle,René Kallies,Jan Tödtmann,Sabine Specht,Marcel A. Müller,Sandra Junglen,Jan Papies,Christian Drosten

doi:10.1186/s12985-016-0531-5

Lukas Ehlen, Isabella Eckerle + Show 7 more

Open Access

https://doi.org/10.1186/s12985-016-0531-5

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Abstract

BackgroundSmall 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.MethodsA 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.ResultsWe 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.ConclusionIn 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.

Highlights

Small mammals such as bats and rodents have been increasingly recognized as reservoirs of novel potentially zoonotic pathogens
There have been a large number of novel, potentially zoonotic viruses that have been shown to be associated with small mammals, especially those of the orders Chiroptera and Rodentia, [4,5,6,7,8,9,10,11,12,13,14]
S. hispidus and associated viruses In order to assess the role of cotton rats as an experimental animal model for viral diseases and as a reservoir of zoonotic viruses in the wild, a review of the literature was performed

Summary

Introduction

Small mammals such as bats and rodents have been increasingly recognized as reservoirs of novel potentially zoonotic pathogens. The isolation and propagation of these novel viruses has been unsuccessful in most instances, which limits further evaluation of their zoonotic risk Upon characterizing these novel viruses, it has become clear that most available animal models such as the domestic mouse or rat are of limited use, as they do not reflect the evolutionary conserved pathogen-host interaction that is a key trait of many reservoir-restricted viruses. In light of the large species range in which novel and potentially zoonotic viruses have been discovered, there remains a need for suitable in vitro models to understand virus-host interactions, interspecies spillover, and general viral pathogenicity [15]. Species-specific cell culture models may serve as acceptable surrogates [16,17,18,19]

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