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Updated: Jun 24, 2025
Monitoring Changes in Human Umbilical Vein Endothelial Cells upon Viral Infection Using Impedance-Based Real-Time Cell Analysis
Published on: May 5, 2023
Risk factors for severe COVID-19 disease increase SARS-CoV-2 infectivity of endothelial cells and pericytes
Luca Biasetti1, Nikos Zervogiannis1, Kira Shaw1
1Sussex Neuroscience, School of Psychology, University of Sussex , East Sussex BN1 9QG, UK.
Insights
Apolipoprotein E4 (APOE4) genotype and inflammation increase severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity in vascular cells. This explains how these factors worsen COVID-19 severity by enhancing viral entry into the vasculature.
Area of Science:
- Vascular Biology
- Infectious Diseases
- Genetics
Background:
- Coronavirus disease 2019 (COVID-19) affects multiple organs, with vascular system involvement being a key factor.
- The apolipoprotein E (APOE) genotype and systemic inflammation are associated with increased COVID-19 severity.
- Understanding the mechanisms of vascular infection is crucial for explaining disease severity.
Purpose of the Study:
- To investigate the impact of apolipoprotein E (APOE) genotype and inflammation on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity in vascular cells.
- To determine if APOE genotype or inflammation influences viral entry into endothelial cells and pericytes.
Main Methods:
- Utilized pseudo-typed SARS-CoV-2 viruses for infection studies.
- Employed targeted replacement human APOE3 and APOE4 mice.
- Induced inflammation using bacterial lipopolysaccharide (LPS) in cultured human and mouse endothelial cells and pericytes.
Main Results:
- SARS-CoV-2 infectivity was higher in murine cerebrovascular pericytes than endothelial cells.
- Cultures expressing the APOE4 allele showed increased viral infectivity compared to APOE3.
- Pre-incubation with LPS significantly enhanced SARS-CoV-2 infectivity in human and mouse pericytes and human endothelial cells.
Conclusions:
- APOE4 genotype and systemic inflammation enhance SARS-CoV-2 infectivity in vascular cells.
- These findings elucidate mechanisms by which risk factors contribute to severe COVID-19.
- Targeting vascular cell infectivity may offer therapeutic strategies for severe COVID-19.
Abstract:
Coronavirus disease 2019 (COVID-19) was initially considered a primarily respiratory disease but is now known to affect other organs including the heart and brain. A major route by which COVID-19 impacts different organs is via the vascular system. We studied the impact of apolipoprotein E (APOE) genotype and inflammation on vascular infectivity by pseudo-typed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses in mouse and human cultured endothelial cells and pericytes. Possessing the APOE4 allele or having existing systemic inflammation is known to enhance the severity of COVID-19. Using targeted replacement human APOE3 and APOE4 mice and inflammation induced by bacterial lipopolysaccharide (LPS), we investigated infection by SARS-CoV-2. Here, we show that infectivity was higher in murine cerebrovascular pericytes compared to endothelial cells and higher in cultures expressing APOE4. Furthermore, increasing the inflammatory state of the cells by prior incubation with LPS increased infectivity into human and mouse pericytes and human endothelial cells. Our findings provide insights into the mechanisms underlying severe COVID-19 infection, highlighting how risk factors such as APOE4 genotype and prior inflammation may exacerbate disease severity by augmenting the virus's ability to infect vascular cells.
