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Quantitative proteomics of hamster lung tissues infected with SARS-CoV-2 reveal host factors having implication in the disease pathogenesis and severity.

ABSTRACT: Syrian golden hamsters (Mesocricetus auratus) infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) manifests lung pathology. In this study, efforts were made to check the infectivity of a local SARS-CoV-2 isolate in a self-limiting and non-lethal hamster model and evaluate the differential expression of lung proteins during acute infection and convalescence. The findings of this study confirm the infectivity of this isolate in vivo. Analysis of clinical parameters and tissue samples show the pathophysiological manifestation of SARS-CoV-2 infection similar to that reported earlier in COVID-19 patients and hamsters infected with other isolates. However, diffuse alveolar damage (DAD), a common histopathological feature of human COVID-19 was only occasionally noticed. The lung-associated pathological changes were very prominent on the 4th day post-infection (dpi), mostly resolved by 14 dpi. Here, we carried out the quantitative proteomic analysis of the lung tissues from SARS-CoV-2-infected hamsters on day 4 and day 14 post-infection. This resulted in the identification of 1585 proteins of which 68 proteins were significantly altered between both the infected groups. Pathway analysis revealed complement and coagulation cascade, platelet activation, ferroptosis, and focal adhesion as the top enriched pathways. In addition, we also identified altered expression of two pulmonary surfactant-associated proteins (Sftpd and Sftpb), known for their protective role in lung function. Together, these findings will aid in understanding the mechanism(s) involved in SARS-CoV-2 pathogenesis and progression of the disease.

SUBMITTER: Suresh V

PROVIDER: S-EPMC8206718 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Quantitative proteomics of hamster lung tissues infected with SARS-CoV-2 reveal host-factors having implication in the disease pathogenesis and severity

Project description:COVID-19 or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), appeared first in Wuhan, Hubei, China, has emerged as a global health concern claiming millions of lives worldwide. Syrian golden hamster (Mesocricetus auratus) has emerged as a suitable model as when infected by SARS-CoV-2, manifests lung pathology resembling human COVID-19 patients. In this study, we employed a quantitative approach to study the proteomic changes in the SARS-CoV-2-infected lung tissue. The samples were analyzed using Orbitrap Fusion Tribrid mass spectrometer in triplicates and the data acquired was searched against Mesocricetus auratus protein database which resulted in the identification of nearly 2,000 non-redundant proteins. The outcome of this study will facilitate in discovery of potential candidate biomarkers for predicting disease course and warrants their further validation in human patient samples.

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