Robert-von-Ostertag-Str. 8
14163 Berlin
Introduction: Of various COVID-19 models, two hamster species are of particular interest. Specifically, the Roborovski dwarf hamster mimics a severe, rapidly lethal pneumonia as seen in highly susceptible patients, whereas the Syrian hamster presents with a moderate, self-limiting disease. Here, we aim to identify relevant mechanisms responsible for the striking differences from a spatial proteomics perspective.
Materials and methods: Hamsters (n = 6) were sacrificed 2 days after intranasal infection with SARS-CoV-2. FFPE lung sections were processed for histology and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Spatial proteomics data were analyzed with SCiLS™ Lab and Enrichr. Molecular signatures were considered discriminatory with area under curve (AUC) values of <0.3 or >0.7, respectively.
Results: In the Roborovski hamster, 15 proteins were of a higher and six of a lower relative abundance when compared to the Syrian hamster. The former included proteins involved in blood coagulation (annexin A2, fibrinogen alpha chain, myosin-9), cell morphology (plectin isoform X16), and wound healing (heat shock protein beta-1). Strikingly, the latter influenced extracellular matrix morphology (fibronectin isoform X1), leucocyte tethering (vimentin) and respiratory burst (40S ribosomal protein S19). Additionally, some proteins (eg, higher albumin) directly correlated with histomorphology (ie, more severe, protein-rich alveolar oedema).
Conclusions: Spatial proteomics enabled the detection of several discriminating proteins, some of which reflected histomorphological findings. However, the data call for future in-depth proteome studies to allow for a more detailed understanding of distinctive pathways or pathogenetic discrepancies that would explain the stark species differences in disease progression.