Ferrets as a Novel Animal Model for Studying Human Respiratory Syncytial Virus Infections in Immunocompetent and Immunocompromised Hosts.
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.
Viroclinics Biosciences, 3029 AK Rotterdam, The Netherlands. stittelaar@viroclinics.com.
Koert J
KJ
Stittelaar
Viroclinics Biosciences, 3029 AK Rotterdam, The Netherlands. dewaal@viroclinics.com.
Leon
L
de Waal
Viroclinics Biosciences, 3029 AK Rotterdam, The Netherlands. amerongen@viroclinics.com.
Geert
G
van Amerongen
Viroclinics Biosciences, 3029 AK Rotterdam, The Netherlands. veldhuiskroeze@viroclinics.com.|Department of Viroscience, Erasmus MC, 3015 CN Rotterdam, The Netherlands. veldhuiskroeze@viroclinics.com.
Edwin J B
EJ
Veldhuis Kroeze
Department of Viroscience, Erasmus MC, 3015 CN Rotterdam, The Netherlands. p.fraaij@erasmusmc.nl.
Pieter L A
PL
Fraaij
Viroclinics Biosciences, 3029 AK Rotterdam, The Netherlands. baalen@viroclinics.com.
Carel A
CA
van Baalen
Department of Viroscience, Erasmus MC, 3015 CN Rotterdam, The Netherlands. j.vankampen@erasmusmc.nl.
Jeroen J A
JJ
van Kampen
Department of Viroscience, Erasmus MC, 3015 CN Rotterdam, The Netherlands. erhard.van.der.vries@tiho-hannover.de.|Research Centre for Emerging Infections and Zoonoses, University of Veterinary Medicine, 30559 Hannover, Germany. erhard.van.der.vries@tiho-hannover.de.
Erhard
E
van der Vries
Viroclinics Biosciences, 3029 AK Rotterdam, The Netherlands. albert.osterhaus@tiho-hannover.de.|Department of Viroscience, Erasmus MC, 3015 CN Rotterdam, The Netherlands. albert.osterhaus@tiho-hannover.de.|Research Centre for Emerging Infections and Zoonoses, University of Veterinary Medicine, 30559 Hannover, Germany. albert.osterhaus@tiho-hannover.de.
Albert D M E
AD
Osterhaus
Department of Viroscience, Erasmus MC, 3015 CN Rotterdam, The Netherlands. r.deswart@erasmusmc.nl.
Rik L
RL
de Swart
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005289:Ferrets; D006651:Histocytochemistry; D016867:Immunocompromised Host; D018357:Respiratory Syncytial Virus Infections / Q000473:pathology* / Q000821:virology*; D018113:Respiratory Syncytial Virus, Human / Q000472:pathogenicity*; D012137:Respiratory System / Q000473:pathology* / Q000821:virology*; D019562:Viral Load
animal models; ferret; immunocompromised host; respiratory syncytial virus; viral loads