Human ACE2 expression, a major tropism determinant for SARS-CoV-2, is regulated by upstream and intragenic elements

PLoS Pathogens, Journal Year: 2023, Volume and Issue: 19(2), P. e1011168 - e1011168

Published: Feb. 22, 2023

Angiotensin-converting enzyme 2 (ACE2), part of the renin-angiotensin system (RAS), serves as an entry point for SARS-CoV-2, leading to viral proliferation in permissive cell types. Using mouse lines which Ace2 locus has been humanized by syntenic replacement, we show that regulation basal and interferon induced ACE2 expression, relative expression levels different transcripts, sexual dimorphism are unique each species, differ between tissues, determined both intragenic upstream promoter elements. Our results indicate higher observed lungs mice humans may reflect fact drives populous airway club cells while human alveolar type (AT2) cells. In contrast transgenic is expressed ciliated under control FOXJ1 promoter, expressing endogenous a robust immune response after infection with rapid clearance virus. This supports model differential determines types lung infected, this turn modulates host outcome COVID-19.

Language: Английский

AC-73 and Syrosingopine Inhibit SARS-CoV-2 Entry into Megakaryocytes by Targeting CD147 and MCT4

Viruses, Journal Year: 2024, Volume and Issue: 16(1), P. 82 - 82

Published: Jan. 4, 2024

Coagulation disorders are described in COVID-19 and long COVID patients. In particular, SARS-CoV-2 infection megakaryocytes, which precursors of platelets involved thrombotic events COVID-19, and, rare cases, vaccinated individuals, requires further investigation, particularly with the emergence new variants. CD147, regulation inflammation required to fight virus infection, can facilitate entry into megakaryocytes. MCT4, a co-binding protein CD147 key player glycolytic metabolism, could also play role infection. Here, we investigated susceptibility megakaryocytes via MCT4. We performed Dami cells human CD34+ hematopoietic progenitor induced megakaryocytic differentiation pseudovirus presence AC-73 syrosingopine, respective inhibitors MCT4 inducers autophagy, process essential megakaryocyte differentiation. Both syrosingopine enhance autophagy during but only enhances maturation. Importantly, found that or significantly inhibits Altogether, our data indicate as be used prevent binding COVID-19-associated coagulopathy.

Language: Английский

Microfluidic Diffusional Sizing (MDS) Measurements of Secretory Neutralizing Antibody Affinity Against SARS-CoV-2

Annals of Biomedical Engineering, Journal Year: 2024, Volume and Issue: 52(6), P. 1653 - 1664

Published: March 8, 2024

Abstract SARS-CoV-2 has rampantly spread around the globe and continues to cause unprecedented loss through ongoing waves of (re)infection. Increasing our understanding protection against infection with is critical ending pandemic. Serological assays have been widely used assess immune responses, but secretory antibodies, essential first line defense, studied only a limited extent. Of particular interest importance are neutralizing which block binding spike protein human receptor angiotensin-converting enzyme-2 (ACE2) thus for defense. Here, we employed Microfluidic Diffusional Sizing (MDS), an immobilization-free technology, characterize antibody affinity receptor-binding domain (RBD) trimer in saliva. Affinity measurement was obtained contrived sample buffer using recombinant RBD monoclonal antibody. Limited saliva samples demonstrated that MDS applies measurement. The ability disrupt complex ACE2-Fc shown. Using quantitative assay on patient sample, determined site concentration antibodies.

Language: Английский