PMID- 34209230 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210727 IS - 2076-0817 (Print) IS - 2076-0817 (Electronic) IS - 2076-0817 (Linking) VI - 10 IP - 7 DP - 2021 Jun 30 TI - Predictive Value of Precision-Cut Lung Slices for the Susceptibility of Three Animal Species for SARS-CoV-2 and Validation in a Refined Hamster Model. LID - 10.3390/pathogens10070824 [doi] LID - 824 AB - In assessing species susceptibility for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and in the search for an appropriate animal model, multiple research groups around the world inoculated a broad range of animal species using various SARS-CoV-2 strains, doses and administration routes. Although in silico analyses based on receptor binding and diverse in vitro cell cultures were valuable, exact prediction of species susceptibility based on these tools proved challenging. Here, we assessed whether precision-cut lung slices (PCLS) could facilitate the selection of animal models, thereby reducing animal experimentation. Pig, hamster and cat PCLS were incubated with SARS-CoV-2 and virus replication was followed over time. Virus replicated efficiently in PCLS from hamsters and cats, while no evidence of replication was obtained for pig PCLS. These data corroborate the findings of many research groups that have investigated the susceptibility of hamsters, pigs and cats towards infection with SARS-CoV-2. Our findings suggest that PCLS can be used as convenient tool for the screening of different animal species for sensitivity to newly emerged viruses. To validate our results obtained in PCLS, we employed the hamster model. Hamsters were inoculated with SARS-CoV-2 via the intranasal route. Susceptibility to infection was evaluated by body weight loss, viral loads in oropharyngeal swabs and respiratory tissues and lung pathology. The broadly used hamster model was further refined by including activity tracking of the hamsters by an activity wheel as a very robust and sensitive parameter for clinical health. In addition, to facilitate the quantification of pathology in the lungs, we devised a semi-quantitative scoring system for evaluating the degree of histological changes in the lungs. The inclusion of these additional parameters refined and enriched the hamster model, allowing for the generation of more data from a single experiment. FAU - Gerhards, Nora M AU - Gerhards NM AD - Wageningen Bioveterinary Research, Houtribweg 39, 8221 RA Lelystad, The Netherlands. FAU - Cornelissen, Jan B W J AU - Cornelissen JBWJ AD - Wageningen Bioveterinary Research, Houtribweg 39, 8221 RA Lelystad, The Netherlands. FAU - van Keulen, Lucien J M AU - van Keulen LJM AD - Wageningen Bioveterinary Research, Houtribweg 39, 8221 RA Lelystad, The Netherlands. FAU - Harders-Westerveen, Jose AU - Harders-Westerveen J AD - Wageningen Bioveterinary Research, Houtribweg 39, 8221 RA Lelystad, The Netherlands. FAU - Vloet, Rianka AU - Vloet R AD - Wageningen Bioveterinary Research, Houtribweg 39, 8221 RA Lelystad, The Netherlands. FAU - Smid, Bregtje AU - Smid B AD - Wageningen Bioveterinary Research, Houtribweg 39, 8221 RA Lelystad, The Netherlands. FAU - Vastenhouw, Stephanie AU - Vastenhouw S AD - Wageningen Bioveterinary Research, Houtribweg 39, 8221 RA Lelystad, The Netherlands. FAU - van Oort, Sophie AU - van Oort S AD - Wageningen Bioveterinary Research, Houtribweg 39, 8221 RA Lelystad, The Netherlands. FAU - Hakze-van der Honing, Renate W AU - Hakze-van der Honing RW AUID- ORCID: 0000-0001-7621-2729 AD - Wageningen Bioveterinary Research, Houtribweg 39, 8221 RA Lelystad, The Netherlands. FAU - Gonzales, Jose L AU - Gonzales JL AUID- ORCID: 0000-0002-7889-5380 AD - Wageningen Bioveterinary Research, Houtribweg 39, 8221 RA Lelystad, The Netherlands. FAU - Stockhofe-Zurwieden, Norbert AU - Stockhofe-Zurwieden N AD - Wageningen Bioveterinary Research, Houtribweg 39, 8221 RA Lelystad, The Netherlands. FAU - de Jong, Rineke AU - de Jong R AD - Wageningen Bioveterinary Research, Houtribweg 39, 8221 RA Lelystad, The Netherlands. FAU - van der Poel, Wim H M AU - van der Poel WHM AUID- ORCID: 0000-0002-7498-8002 AD - Wageningen Bioveterinary Research, Houtribweg 39, 8221 RA Lelystad, The Netherlands. FAU - Vreman, Sandra AU - Vreman S AD - Wageningen Bioveterinary Research, Houtribweg 39, 8221 RA Lelystad, The Netherlands. FAU - Kortekaas, Jeroen AU - Kortekaas J AUID- ORCID: 0000-0002-0329-0176 AD - Wageningen Bioveterinary Research, Houtribweg 39, 8221 RA Lelystad, The Netherlands. AD - Laboratory of Virology, Wageningen University, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands. FAU - Wichgers Schreur, Paul J AU - Wichgers Schreur PJ AUID- ORCID: 0000-0001-9790-2438 AD - Wageningen Bioveterinary Research, Houtribweg 39, 8221 RA Lelystad, The Netherlands. FAU - Oreshkova, Nadia AU - Oreshkova N AD - Wageningen Bioveterinary Research, Houtribweg 39, 8221 RA Lelystad, The Netherlands. LA - eng GR - WOT-01-003-083/Ministerie van Landbouw, Natuur en Voedselkwaliteit/ GR - KB-21-006-036/Ministerie van Landbouw, Natuur en Voedselkwaliteit/ GR - not applicable/Coalition for Epidemic Preparedness Innovations/ PT - Journal Article DEP - 20210630 PL - Switzerland TA - Pathogens JT - Pathogens (Basel, Switzerland) JID - 101596317 PMC - PMC8308566 OTO - NOTNLM OT - SARS-CoV-2 OT - activity OT - hamster model OT - histology scores OT - precision-cut lung slices COIS- The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. EDAT- 2021/07/03 06:00 MHDA- 2021/07/03 06:01 PMCR- 2021/06/30 CRDT- 2021/07/02 01:37 PHST- 2021/05/08 00:00 [received] PHST- 2021/06/20 00:00 [revised] PHST- 2021/06/27 00:00 [accepted] PHST- 2021/07/02 01:37 [entrez] PHST- 2021/07/03 06:00 [pubmed] PHST- 2021/07/03 06:01 [medline] PHST- 2021/06/30 00:00 [pmc-release] AID - pathogens10070824 [pii] AID - pathogens-10-00824 [pii] AID - 10.3390/pathogens10070824 [doi] PST - epublish SO - Pathogens. 2021 Jun 30;10(7):824. doi: 10.3390/pathogens10070824.