Ferrets as a Novel Animal Model for Studying Human Respiratory Syncytial Virus Infections in Immunocompetent and Immunocompromised Hosts

Viruses

Jeroen J.A. van Kampen¹  Pieter L.A. Fraaij¹  Erhard van der Vries¹  Rik L. de Swart¹  Geert van Amerongen²  Edwin J.B. Veldhuis Kroeze²  Koert J. Stittelaar²  Carel A. van Baalen²  Leon de Waal²  Albert D.M.E. Osterhaus² 

[1] Department of Viroscience, Erasmus MC, 3015 CN Rotterdam, The Netherlands;Viroclinics Biosciences, 3029 AK Rotterdam, The Netherlands;

关键词: respiratory syncytial virus;    animal models;    ferret;    viral loads;    immunocompromised host;   

DOI  :  10.3390/v8060168

来源: DOAJ

【 摘 要 】

Human respiratory syncytial virus (HRSV) is an important cause of severe respiratory tract disease in immunocompromised patients. Animal models are indispensable for evaluating novel intervention strategies in this complex patient population. To complement existing models in rodents and non-human primates, we have evaluated the potential benefits of an HRSV infection model in ferrets (Mustela putorius furo). Nine- to 12-month-old HRSV-seronegative immunocompetent or immunocompromised ferrets were infected with a low-passage wild-type strain of HRSV subgroup A (105 TCID50) administered by intra-tracheal or intra-nasal inoculation. Immune suppression was achieved by bi-daily oral administration of tacrolimus, mycophenolate mofetil, and prednisolone. Throat and nose swabs were collected daily and animals were euthanized four, seven, or 21 days post-infection (DPI). Virus loads were determined by quantitative virus culture and qPCR. We observed efficient HRSV replication in both the upper and lower respiratory tract. In immunocompromised ferrets, virus loads reached higher levels and showed delayed clearance as compared to those in immunocompetent animals. Histopathological evaluation of animals euthanized 4 DPI demonstrated that the virus replicated in the respiratory epithelial cells of the trachea, bronchi, and bronchioles. These animal models can contribute to an assessment of the efficacy and safety of novel HRSV intervention strategies.

【 授权许可】

Unknown