Canadian Journal of Infectious Diseases and Medical Microbiology (Jan 2023)

ERC-BiP Functional Protein Pathway for Assessing Endoplasmic Reticulum Stress Induced by SARS-CoV-2 Replication after Cell Invasion

  • Mingshan Xue,
  • Zhiwei Lin,
  • Teng Zhang,
  • Zhangkai J. Cheng,
  • Runpei Lin,
  • Baojun Guo,
  • Yifeng Zeng,
  • Fengyu Hu,
  • Feng Li,
  • Peiyan Zheng,
  • Huimin Huang,
  • Ning Li,
  • Qi Zhao,
  • Baoqing Sun,
  • Xiaoping Tang

DOI
https://doi.org/10.1155/2023/7253779
Journal volume & issue
Vol. 2023

Abstract

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Background. SARS-CoV-2 induces apoptosis and amplifies the immune response by continuously stressing the endoplasmic reticulum (ER) after invading cells. This study aimed to establish a protein-metabolic pathway associated with ER dysfunction based on the invasion mechanism of SARS-CoV-2. Methods. This study included 17 healthy people and 46 COVID-19 patients, including 38 mild patients and 8 severe patients. Proteomics and metabolomics were measured in the patient plasma collected at admission and one week after admission. The patients were further divided into the aggravation and remission groups based on disease progression within one week of admission. Results. Cross-sectional comparison showed that endoplasmic reticulum molecular chaperone-binding immunoglobulin protein (ERC-BiP), angiotensinogen (AGT), ceramide acid (Cer), and C-reactive protein (CRP) levels were significantly increased in COVID-19 patients, while the sphingomyelin (SM) level was significantly decreased P < 0.05. In addition, longitudinal comparative analysis found that the temporal fold changes of ERC-BiP, AGT, Cer, CRP, and SM were significantly different between the patients in the aggravation and remission groups P < 0.05. ERC-BiP, AGT, and Cer levels were significantly increased in aggravation patients, while SM was significantly decreased P < 0.05. Meanwhile, ERC-BiP was significantly correlated with AGT (r = 0.439; P < 0.001). Conclusions. ERC-BiP can be used as a core index to reflect the degree of ER stress in COVID-19 patients, which is of great value for evaluating the functional state of cells. A functional pathway for AGT/ERC-BiP/glycolysis can directly assess the activation of unfolded protein reactions. The ERC-BiP pathway is closer to the intracellular replication pathway of SARS-CoV-2 and may help in the development of predictive protocols for COVID-19 exacerbation.