Investigations upon the virus-host interaction of the bluetongue disease
Final Report Abstract
Bluetongue virus (BTV) is a double stranded RNA virus and causes severe haemorrhagic fever-like disease in sheep, while other ruminants like goats and cows show less severe symptoms. The arthropod-borne virus causes viraemia in all ruminant species and until now it is not clear, what are the major determinants leading to severe disease in some species while others were less or not effected. The aim of this study was to investigate the molecular mechanisms distinguishing the specific immune response of susceptible and resilient hosts. Therefore, sheep were experimentally infected with BTV-1 from field outbreaks in 2006 and 2013, respectively, as well as with BTV-8 alongside control animals. Results show that the used viruses cause a different severity of disease in sheep with BTV-1 2006 showing most severe symptoms including severe subcutaneous oedema and respiratory symptoms leading to death. While BTV-8 infected animals hardly showed any clinical signs, sheep infected with BTV-1 2013 showed moderate clinical symptoms including nasal discharge and ulceration of the nares as well as respiratory symptoms. Conclusively, it was possible to identify a unique clinical phenotype for each BTV virus strain in sheep. Subsequent downstream analyses showed differences in the interferon response in the blood as well as changes in the blood chemistry and haematology for each virus. Viral RNA was detected in the blood (by RT-qPCR) and increased starting from 1 day post infection. Next generation sequencing for molecular phenotyping of the transcriptome from blood samples was planned for the time points 0, 1, 3 and 7 days post infection. Due to the Coronavirus pandemic this had to be delayed for 1 year and the results will be finalised soon. Furthermore, the initially planned species comparison of the species-specific immune response in sheep and goat upon BTV infection had to be postponed due to the pandemic. Following the regulations of the local authorities (Scottish government) research was restricted to investigations focussing on Systemic Acute Respiratory Syndrome (SARS) Coronavirus-2. Therefore, I took the chance and focussed my work on the Covid-19. Firstly, I established several methods to detect SARS CoV-2 specific RNA and protein in tissue culture systems as well as in formalin-fixed and paraffin-embedded tissues. Since March 2020, I studied the pathogenesis of Covid-19 in vitro and ex vivo. In one study, I contributed to a study establishing a toolkit to detect and work with the virus in vitro. In another study, I applied the methods to detect viral RNA and protein in a feline case of Covid-19. In an in vitro co-infection study, we investigated the role of another respiratory virus (Rhinovirus) during the infection with SARS CoV-2 in a three-dimensional cell culture model (air liquid interface cultures). A recent ongoing research project instigates the role of elevated temperatures on the growth kinetics of SARS Coronavirus-2 and associated gene profiles explaining the reduced viral replication at higher temperatures. https://metro.co.uk/2021/03/23/inside-the-glasgow-lab-studying-covid-for-a-global-research-project-14291897/
Publications
- A plasmid DNA-launched SARS-CoV-2 reverse genetics system and coronavirus toolkit for COVID-19 research. PLoS Biol. 2021 Feb 25;19(2):e3001091
Rihn SJ, ..., Herder V, ..., Mahalingam S
(See online at https://doi.org/10.1371/journal.pbio.3001091) - Detection of SARS-CoV-2 in respiratory samples from cats in the UK associated with human-to-cat transmission. Vet Rec. 2021 Apr;188(8):e247
Hosie MJ, Epifano I, Herder V, Orton RJ, Stevenson A, Johnson N, MacDonald E, Dunbar D, McDonald M, Howie F, Tennant B, Herrity D, Da Silva Filipe A, Streicker DG; COVID-19 Genomics UK (COG-UK) consortium, Willett BJ, Murcia PR, Jarrett RF, Robertson DL, Weir W
(See online at https://doi.org/10.1002/vetr.247) - Human rhinovirus infection blocks SARS-CoV-2 replication within the respiratory epithelium: implications for COVID-19 epidemiology. J Infect Dis. 2021 Mar 23:jiab147
Dee K, Goldfarb DM, Haney J, Amat JAR, Herder V, Stewart M, Szemiel AM, Baguelin M, Murcia PR
(See online at https://doi.org/10.1093/infdis/jiab147) - Vascular inflammation is associated with loss of aquaporin 1 expression on endothelial cells and increased fluid leakage in SARS-CoV-2 infected golden Syrian hamsters. Viruses 2021, 13(4), 639
Lisa Allnoch, Georg Beythien, Eva Leitzen, Kathrin Becker, Franz-Josef Kaup, Stephanie Stanelle-Bertram, Berfin Schaumburg, Nancy Mounogou Kouassi, Sebastian Beck, Martin Zickler, Vanessa Herder, Gülsah Gabriel, Wolfgang Baumgärtner
(See online at https://doi.org/10.3390/v13040639)
