Quantitative tissue proteomics reveals increased pathogenesis associated with infection with the SARS-CoV-2 Delta variant that is independent of viral infectivity in Syrian golden hamsters

ABSTRACT: Background: Since its emergence in 2020, circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been dominated by waves of genetically distinct variants with varying pathogenicity. Understanding the molecular mechanisms underlying SARS-CoV-2 pathogenesis, and the host and viral determinants driving pathogenesis, is critical for developing therapies to prevent severe illness and death. Methods: Syrian golden hamsters were infected with an ancestral variant (WA-1/2020), a Delta variant (B.1.617.2), and an early Omicron variant (BA.1) of SARS-CoV-2, and host responses in multiple tissues were compared to tissues collected from mock-infected animals at day five post-infection. We conducted quantitative proteomics, phosphoproteomics, histology, and immunofluorescent staining to assess differences in pathogenicity between the variants. Findings: We observed the greatest weight loss in hamsters infected with the Delta variant compared to the WA-1 and Omicron variants, while the viral protein quantified in all tissues was highest for the WA-1 variant, followed by Delta, then Omicron. Evaluation of tissues revealed that infection with the Delta variant was associated with decreased cilia proteins in trachea, increased fibrinolysis and blood coagulation protein signatures in lung, and increased immune cell infiltration, edema, and airway blockage in the lung. Interpretation: Despite multiple indications of greater pathogenesis associated with infection with the Delta variant, this was not due to greater infectivity of the Delta variant. These findings suggest that there are intrinsic viral determinants that promote pathogenesis independent of infectivity. A more pronounced loss of cilia in the trachea and increased lung pathologic features associated with the Delta variant may lead to co-infections and co-morbidities that are major risk factors for severe illness and death.

INSTRUMENT(S):

ORGANISM(S): Mesocricetus Auratus (golden Hamster)

TISSUE(S): Lung

SUBMITTER: Jeffrey Johnson  

LAB HEAD: Jeffrey Johnson

PROVIDER: PXD054808 | Pride | 2026-01-26

REPOSITORIES: Pride