Single Cell RNAseq and VDJ sequence of ACE2 reactive and non-reactive B-cells isolated from COVID-19 patients peripheral blood
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE178123 | GEO | 2023/06/01
REPOSITORIES: GEO
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Project description:The Angiotensin-converting enzyme 2 (ACE2) receptor is the central entry point for SARS-Cov2. Several SAR-Cov2 substrains have developed mutations in their spike protein to maximize their use of ACE2, e.g. to strengthen ACE2 binding for increased uptake or adapt to specific amino acid properties of ACE2 to cross the species barrier. But little is known about the effect of host regulators on ACE2 and subsequently their impact on SARS-Cov2 infection. Here we identify the E3 ligase MDM2 as a ACE2 modulator. The knockout of MDM2 induced a strong pro-viral effect specific for SARS-Cov2 and we could see the increase of ACE2 levels. This effect is likely dependent on the ubiquitination site Lysine 788, which MDM2 uses to induce proteasomal degradation of ACE2. Substituting this amino acid led to increased ACE2 levels and increased SARS-CoV2 infection facilitated by enhanced SARS-Cov2 uptake.
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Project description:Background: The first step in SARS-CoV-2 infection is binding of the virus to angiotensin converting enzyme 2 (ACE2) on the airway epithelium. Asthma affects over 300 million people world-wide, many of whom may encounter SARS-CoV-2. Epidemiologic data suggests that asthmatics who get infected may be at increased risk of more severe disease. Our objective was to assess whether maintenance inhaled corticosteroids (ICS), a major treatment for asthma, is associated with airway ACE2 expression in asthmatics. Methods: Large airway epithelium (LAE) of asthmatics treated with maintenance ICS (ICS+), asthmatics not treated with ICS (ICS-), and healthy controls (controls) was analyzed for expression of ACE2 and other coronavirus infection-related genes using microarrays. Results: AsResults: As a group, there was no difference in LAE ACE2 expression in all asthmatics vs controls. In contrast, subgroup analysis demonstrated that LAE ACE2 expression was higher in asthmatics ICS+ compared to ICS‾ and ACE2 expression was higher in male ICS+ compared to female ICS+ and ICS‾ of either sex. ACE2 expression did not correlate with serum IgE, absolute eosinophil level, or change in FEV1 in response to bronchodilators in either ICS- or ICS+. Conclusion: Airway ACE2 expression is increased in asthmatics on long-term treatment with ICS, an observation that should be taken into consideration when assessing the use of inhaled corticosteroids during the pandemic. a group, there was no difference in LAE ACE2 expression in all asthmatics vs controls. In contrast, subgroup analysis demonstrated that LAE ACE2 expression was higher in asthmatics ICS+ compared to ICS‾ and ACE2 expression was higher in male ICS+ compared to female ICS+ and ICS‾ of either sex. ACE2 expression did not correlate with serum IgE, absolute eosinophil level, or change in FEV1 in response to bronchodilators in either ICS- or ICS+. Conclusion: Airway ACE2 expression is increased in asthmatics on long-term treatment with ICS, an observation that should be taken into consideration when assessing the use of inhaled corticosteroids during the pandemic.
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