The dsRNA-proximal proteome during SARS-CoV-2 infection

ABSTRACT: Coronaviruses establish replication organelles to synthesize their RNAs while evading host defenses. To systematically profile the host factors and the dynamic interplay between viral and host factors during viral replication, we develop an antibody-based proximity labeling strategy targeting double-stranded RNA (dsRNA), a hallmark of coronavirus replication intermediates, to map the proximal proteome at viral replication sites. Applying this to SARS-CoV-2–infected Calu-3 and HCoV-OC43–infected HCT-8, we reveal both conserved requirements and unique adaptations in each virus. Profiling during the early stage of SARS-CoV-2 infection further uncovers dynamic recruitment patterns: an early enrichment of ER proteins, mitochondrial proteins and RNA processing factors, and a progressive exclusion of stress granule components. Functional analyses of RNA-binding proteins identify regulatory host factors, including the double-stranded RNA-binding protein STAU1, which plays a pro-viral role on SARS-CoV-2 at the early infection stage. Collectively, these findings establish a robust proteomic framework for investigating coronavirus replication biology and uncover virus-specific strategies to manipulate host cellular machinery.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

SUBMITTER: Sunghan Lee  

LAB HEAD: V. Narry Kim

PROVIDER: PXD069353 | Pride | 2026-07-27

REPOSITORIES: Pride