Stimulus-specific Immune Modulation by SARS-CoV-2 Nucleocapsid Correlates with Severe COVID-19

ABSTRACT: A significant proportion of patients with COVID-19 disease, caused by SARS-CoV-2, develop acute respiratory distress syndrome characterized by pro-inflammatory cytokine secretion and dampened IFN-mediated antiviral response. To uncover the mechanisms by which SARS-CoV-2 drives this dysregulation, we conducted transcriptomic profiling of N-expressing monocyte-derived macrophages treated with different stimuli that activates several pattern recognition receptors. To capture differences in immunoinflammatory responses to different SARS-CoV-2 Nucleocapsids, we performed a comparative proteomics analysis between the hyper inflammatory Delta N protein and less inflammatory Omicron N protein. Both Nucleocapsids expressed in monocyte-derived macrophages were pulled down for affinity purification mass spectrometry (APMS) and their differential protein interactors were identified; revealing Delta N interacts more strongly with stress granule proteins compared to Omicron N, which may explain Delta N pro-inflammatory phenotype. This project was a collaboration between the labs of Dr. Melody Li, Dr. Alexander Hoffmann, and Dr. Mehdi Bouhaddou at UCLA.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human) Severe Acute Respiratory Syndrome Coronavirus 2

TISSUE(S): Macrophage

DISEASE(S): Covid-19

SUBMITTER: Mehdi Bouhaddou  

LAB HEAD: Mehdi Bouhaddou

PROVIDER: PXD067631 | Pride | 2026-06-25

REPOSITORIES: Pride