Quantitative Tissue Proteomics Reveals Protein Signatures Associated with SARS-CoV‑2 Variant Infection in Hamsters

Since its emergence in 2019, circulating SARS-CoV-2 has
been dominated
by waves of genetically distinct variants with varying pathogenicity.
Understanding the multidimensional responses to SARS-CoV-2 infection
and their associations with pathogenesis is critical for developing
therapies to prevent severe illness and death. Here, we applied quantitative
proteome and phosphoproteome analyses to compare host responses to
infections with an ancestral variant (WA-1/2020), a Delta variant
(B.1.617.2), and an Omicron variant (BA.1) of SARS-CoV-2 in Syrian
golden hamster tissues at 5 days postinfection, when peak inflammatory
responses were observed. As has been observed by others, animals infected
with the Delta variant lost more weight than those infected with other
variants, and this effect was associated with decreased cilia proteins
in the trachea tissue and increased signatures of fibrosis in lung
tissue. Phosphoproteome analysis revealed a downregulation of Raf-MEK-ERK
signaling across all variants, suggesting a suppressed proliferative
response in tissues following SARS-CoV-2 infection. These data provide
critical in vivo confirmation of observations from in vitro studies
and provide a quantitative tissue- and SARS-CoV-2 variant-specific
resource of proteome and phosphoproteome responses.