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Metabolic dyshomeostasis induced by SARS-CoV-2 structural proteins reveals immunological insights into viral

Mercedes Lachén-Montes1,2, Naroa Mendizuri1,2, Karina Ausín2,3

  • 1Clinical Neuroproteomics Unit, Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), Pamplona, Spain.

Frontiers in Immunology
|September 26, 2022
PubMed

Insights

SARS-CoV-2 structural proteins (M, N, E, S) disrupt olfactory bulb cells, causing metabolic changes and inflammation. This research reveals how these viral proteins contribute to smell loss in COVID-19 patients.

Area of Science:

  • Neuroscience
  • Virology
  • Immunology

Background:

  • Sudden loss of smell is a common COVID-19 symptom.
  • SARS-CoV-2 has been found in the olfactory bulb (OB), suggesting a direct impact on smell function.

Purpose of the Study:

  • To investigate the molecular effects of SARS-CoV-2 structural proteins (M, N, E, S) on mouse OB cells.
  • To understand the specific roles of each viral protein in olfactory dysfunction and inflammation.

Main Methods:

  • Expressed GFP-tagged SARS-CoV-2 structural proteins in mouse OB cells.
  • Performed transcriptomic and proteomic analyses to characterize molecular changes.
  • Utilized machine learning for proteotranscriptomic data integration.

Main Results:

  • SARS-CoV-2 proteins induced widespread metabolic remodeling, affecting extracellular matrix, lipid metabolism, and tyrosine kinase signaling.
  • Each viral protein exhibited unique molecular interactions and affected cell survival and immune responses.
  • TGF-beta signaling was identified as a key convergence point activated by the viral proteome.

Conclusions:

  • SARS-CoV-2 structural proteins possess immunomodulatory properties beyond virion formation.
  • These findings offer mechanistic insights into olfactory inflammation and smell loss associated with COVID-19.
Keywords:
SARS-CoV-2bioinformaticsimmune responseproteomicssmelltranscriptomics

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