Abstract Title
Development of an ex vivo model to study the zoonotic transmission of noroviruses
Presenter
Nele Villabruna, University of Veterinary Medicine Hanover
Co-Author(s)
Nele Villabruna1,2, Silke Rautenschlein3, Holger Volk4, Isabel Hennig-Pauka5, Andreas Beineke2, Gisa Gerold6
1 Institute for Biochemistry and Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, 30559 Hannover, Germany
2 Institute of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany
3 Clinic for Poultry, University of Veterinary Medicine Hannover, 30559 Hannover, Germany
4 Clinic for Small Animals, University of Veterinary Medicine Hannover, 30559 Hannover, Germany
5 Field Station for Epidemiology (Bakum), University of Veterinary Medicine Hannover, 49456 Bakum, Germany
6 Institute of Virology, Medical University of Innsbruck, Innsbruck, Austria
Abstract Category
Entry and Replication
Abstract
Norovirus is a diverse virus genus, infecting a broad host range of species including wild and domestic animals. New noroviruses frequently emerge, and their origin is unknown. One hypothesis is that noroviruses are transmitted between humans and animals, with animals acting as a reservoir for new noroviruses. To study norovirus interspecies transmission barriers and host susceptibility factors, we established precision-cut intestinal slices (PCIS) of porcine, canine, and avian origin.
Using these PCIS, we show that virus-like particles of human norovirus GII.4 bind to and are subsequently internalized into porcine and canine intestinal tissue to a degree comparable to that of porcine and canine noroviruses, respectively. None of the human or animal norovirus VLPs attached to avian PCIS. GII.4 attachment varied between different sections of the intestine (Duodenum, Jejunum, and Ileum) and was increased under hypoxic conditions. When investigating known norovirus susceptibility factors, we found that blocking the α-fucose group of the histo-blood group antigens (HBGAs) inhibited GII.4 attachment to porcine but not canine PCIS. In contrast, the addition of bile acid did not affect GII.4 binding or internalization in either porcine or canine PCIS. GII.4 as well as the porcine transmissible gastroenteritis virus (TGEV) replicated to some degree in pig PCIS with some donor variation.
In conclusion, we show in an animal experiment replacement model that human norovirus attaches to and replicates in intestinal tissue of pigs but not chickens, suggesting that pigs are susceptible to human norovirus infection and might be an animal reservoir for human noroviruses.
Using these PCIS, we show that virus-like particles of human norovirus GII.4 bind to and are subsequently internalized into porcine and canine intestinal tissue to a degree comparable to that of porcine and canine noroviruses, respectively. None of the human or animal norovirus VLPs attached to avian PCIS. GII.4 attachment varied between different sections of the intestine (Duodenum, Jejunum, and Ileum) and was increased under hypoxic conditions. When investigating known norovirus susceptibility factors, we found that blocking the α-fucose group of the histo-blood group antigens (HBGAs) inhibited GII.4 attachment to porcine but not canine PCIS. In contrast, the addition of bile acid did not affect GII.4 binding or internalization in either porcine or canine PCIS. GII.4 as well as the porcine transmissible gastroenteritis virus (TGEV) replicated to some degree in pig PCIS with some donor variation.
In conclusion, we show in an animal experiment replacement model that human norovirus attaches to and replicates in intestinal tissue of pigs but not chickens, suggesting that pigs are susceptible to human norovirus infection and might be an animal reservoir for human noroviruses.