ACE2 downregulation in olfactory mucosa: Eosinophilic rhinosinusitis as COVID-19 protective factor?
Ontology highlight
ABSTRACT:
SUBMITTER: Marin C
PROVIDER: S-EPMC8222895 | biostudies-literature | 2021 Sep
REPOSITORIES: biostudies-literature
Publications
ACE2 downregulation in olfactory mucosa: Eosinophilic rhinosinusitis as COVID-19 protective factor?
Marin Concepció C Tubita Valeria V Langdon Cristóbal C Fuentes Mireya M Rojas-Lechuga María Jesús MJ Valero Antonio A Alobid Isam I Mullol Joaquim J
Allergy 20210528 9
Similar Datasets
Project description:ACE2 on epithelial cells is the SARS-CoV-2 entry receptor. Single-cell RNA-sequencing data derived from two COVID-19 cohorts revealed that MAP4K3/GLK-positive epithelial cells were increased in patients. SARS-CoV-2-induced GLK overexpression in epithelial cells correlated with COVID-19 severity and vesicle secretion. GLK overexpression induced the epithelial cell-derived exosomes containing ACE2; the GLK-induced exosomes transported ACE2 proteins to recipient cells, facilitating pseudovirus infection. Consistently, ACE2 proteins were increased in the serum exosomes from another COVID-19 cohort. Remarkably, SARS-CoV-2 spike protein stimulated GLK, and GLK stabilized ACE2 in epithelial cells. Mechanistically, GLK phosphorylated ACE2 at two serine residues (Ser776, Ser783), leading to dissociation of ACE2 from its E3 ligase UBR4. Reduction of UBR4-induced Lys48-linked ubiquitination at three lysine residues (Lys26, Lys112, Lys114) of ACE2 prevented its degradation. Furthermore, SARS-CoV-2 pseudovirus or live virus infection in humanized ACE2 mice induced GLK and ACE2 protein levels, as well as ACE2-containing exosomes. Collectively, ACE2 stabilization by SARS-CoV-2-induced MAP4K3/GLK may contribute to the pathogenesis of COVID-19.
| S-SCDT-EMM-2022-15904 | biostudies-other
Project description: Not available
| S-EPMC7675498 | biostudies-literature
Project description:BackgroundRecent numerous epidemiology and clinical association studies reported that ApoE polymorphism might be associated with the risk and severity of coronavirus disease 2019 (COVID-19), and yielded inconsistent results. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection relies on its spike protein binding to angiotensin-converting enzyme 2 (ACE2) receptor expressed on host cell membranes.MethodsA meta-analysis was conducted to clarify the association between ApoE polymorphism and the risk and severity of COVID-19. Multiple protein interaction assays were utilized to investigate the potential molecular link between ApoE and the SARS-CoV-2 primary receptor ACE2, ApoE and spike protein. Immunoblotting and immunofluorescence staining methods were used to access the regulatory effect of different ApoE isoform on ACE2 protein expression.ResultsApoE gene polymorphism (ε4 carrier genotypes VS non-ε4 carrier genotypes) is associated with the increased risk (P = 0.0003, OR = 1.44, 95% CI 1.18-1.76) and progression (P < 0.00001, OR = 1.85, 95% CI 1.50-2.28) of COVID-19. ApoE interacts with both ACE2 and the spike protein but did not show isoform-dependent binding effects. ApoE4 significantly downregulates ACE2 protein expression in vitro and in vivo and subsequently decreases the conversion of Ang II to Ang 1-7.ConclusionsApoE4 increases SARS-CoV-2 infectivity in a manner that may not depend on differential interactions with the spike protein or ACE2. Instead, ApoE4 downregulates ACE2 protein expression and subsequently the dysregulation of renin-angiotensin system (RAS) may provide explanation by which ApoE4 exacerbates COVID-19 disease.
| S-EPMC9910247 | biostudies-literature
Project description:The aim of the present study is to detect the presence of SARS-CoV-2 of patients affected by COVID-19 in olfactory mucosa (OM), sampled with nasal brushing (NB) and biopsy, and to assess whether a non-invasive procedure, such as NB, might be used as a large-scale procedure for demonstrating SARS-CoV-2 presence in olfactory neuroepithelium. Nasal brushings obtained from all the COVID-19 patients resulted positive to SARS-CoV-2 immunocytochemistry while controls were negative. Double immunofluorescence showed that SARS-CoV-2 positive cells included supporting cells as well as olfactory neurons and basal cells. OM biopsies showed an uneven distribution of SARS-CoV-2 positivity along the olfactory neuroepithelium, while OM from controls were negative. SARS-CoV-2 was distinctively found in sustentacular cells, olfactory neurons, and basal cells, supporting what was observed in NB. Ultrastructural analysis of OM biopsies showed SARS-CoV-2 viral particles in the cytoplasm of sustentacular cells. This study shows the presence of SARS-CoV-2 at the level of the olfactory neuroepithelium in patients affected by COVID-19. For the first time, we used NB as a rapid non-invasive tool for assessing a potential neuroinvasion by SARS-CoV-2 infection.
| S-EPMC9004784 | biostudies-literature
Project description:Describe the transcriptomic profile of Golden Hamster olfactory bulb in response to SARS-CoV-2 infection, separating by sexes.
2021-06-19 | E-MTAB-10442 | biostudies-arrayexpress
Project description:BackgroundOlfactory dysfunction (OD) is associated with both post-viral and inflammatory etiologies such as COVID-19 and chronic rhinosinusitis/rhinitis (CRS/R) respectively, to result in reduced quality of life (QoL). However, the former typically induces a sudden-onset OD while the latter has a gradual presentation. This study aims to establish and compare health utility values (HUVs) and olfactory-specific QoL measurements between patients with COVID-19 and CRS/R related OD.MethodsThis prospective study surveyed COVID-19 and CRS/R patients with self-reported OD using HUV assessments (EuroQol-visual analog scale [EQ-VAS], EuroQol-5 dimension [EQ-5D], time trade-off [TTO]) and olfactory and sinonasal QoL measures (questionnaire of olfactory disorders -negative and positive statements [QOD-NS + PS] and sino-nasal outcome test [SNOT-22]). A subgroup of subjects completed objective olfactory testing. Intergroup mean scores were compared using Mann-Whitney U tests.ResultsOne hundred eleven subjects were enrolled: mean age ± SD (43.0 ± 15.4 years), 55.9% female. CRS/R was associated with lower HUVs as measured by EQ-VAS (CRS/R: 0.67 ± 0.18 vs. COVID-19: 0.74 ± 0.19, p = .03) and worse SNOT-22 scores in both overall (CRS/R: 49.03 ± 21.04 vs. COVID-19: 27.58 ± 18.45, p < .001) and subgroup analysis of objectively confirmed OD subjects (CRS/R: 52.40 ± 22.78 vs. COVID-19: 29.84 ± 21.10, p = .01). On the other hand, COVID-19 has greater burden on olfactory-specific QoL (QOD-NS + PS, COVID-19: 23.19 ± 13.73 vs. CRS/R: 17.25 ± 11.38, p = .04). Both groups demonstrated a similar decrease in health using the EQ-5D assessment.ConclusionCRS/R associated OD has a more severe impact on general health and sinonasal specific QoL outcomes, while COVID-19 associated OD has a greater burden on olfactory-specific QoL.Level of evidenceLevel 2c.
| S-EPMC9538416 | biostudies-literature
Project description:The outbreak of coronavirus disease 2019 (COVID-19) has posed a severe threat to global health management system since it has been detected in the human body. This pandemic was prompted by severe acute respiratory syndrome coronaviruses 2 (SARS-CoV-2) and rapidly developed into a public emergency with an alarming increase in cases and deaths. The increasing explorations to SARS-CoV-2 infection guide us to consider whether bone lesion is followed by this pathologic process. We especially focus on the underlying pathobiology that SARS-CoV-2 possibly mediated in bone remodeling and analyze the association of bone destruction with ACE2 in COVID-19 incidence, for preferable understanding the pathogenesis and providing necessary clinical management in orthopedics.
| S-EPMC7416709 | biostudies-literature
Project description:A subset of COVID-19 patients exhibit altered olfactory function. Here we analyze bulk and single cell RNA-Seq datasets to identify cell types in the olfactory epithelium and olfactory bulb that express cell entry molecules that mediate infection by SARS-CoV-2 (CoV-2), the causal agent in COVID-19. We find that samples from whole olfactory mucosa in species including mouse and human express two key genes involved in CoV-2 entry, ACE2 and TMPRSS2. However, neither olfactory sensory neurons nor olfactory bulb neurons express these genes, which are instead expressed in support cells, stem cells, and perivascular cells. These findings suggest that CoV-2 infection of non-neuronal cell types leads to anosmia and related disturbances in odor perception in COVID-19 patients.
2020-07-30 | GSE151346 | GEO
Project description:Several humanized ACE2 (hACE2) mouse models have been developed for COVID-19 studies. Insertion of hACE2 at mouse Ace2 locus enables the utilization of endogenous promoter to drive its expression, better reflecting ACE2 abundance in various cell types and tissues. However, the relatively low expression of hACE2 in these mice may limit their fidelity in mimicking COVID-19 manifestations in humans and hinder their application in viral studies. In this study, we generated four hACE2 mouse models using different strategies for hACE2 expression. We found that the position of the β-globin intron within hACE2 cassette could have contrasting effects on hACE2 expression, with its placement downstream of hACE2 significantly increasing its transcription. Western blot analysis demonstrated that optimizing hACE2 codon usage further enhanced translation efficiency from all tested tissue. Consistent with elevated hACE2 expression, opt-hACE2 mice displayed more active immune response and severe COVID-19 phenotypes following SARS-CoV-2 challenging compared to other hACE2 mouse models. Thus, our study has elucidated the dual role of β-globin element in transgene expression, and highlighted that mice with optimized hACE2 codon preference could serve as a better model for SARS-CoV-2 studies.
2025-02-12 | GSE271163 | GEO
Project description:BackgroundOlfactory-specific quality of life (QOL) can be measured using the Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS), which examines various aspects of olfactory dysfunction. It is unknown if certain factors of the QOD-NS differentially impact QOL.MethodsPatients with chronic rhinosinusitis (CRS) completed the QOD-NS, 22-item Sino-Nasal Outcome Test (SNOT-22), Medical Outcomes Study Short Form 6-D (SF-6D) health utility measure, and Patient Health Questionnaire-2 (PHQ-2) depression screen. Exploratory factor analysis of the QOD-NS was performed. Associations between QOD-NS factors and other QOL metrics were analyzed before and after endoscopic sinus surgery (ESS).ResultsOutcomes were examined on 132 patients. The QOD-NS contains 4 distinct factors. There was no difference in associations between the different factors and baseline clinical characteristics. ESS had greatest effect size (d) on factors 2 and 4 (d = 0.29 and 0.27, respectively, p < 0.05). Postsurgical changes in the SF-6D and SNOT-22 had the strongest correlation with factor 2 scores (r = 0.29 and 0.34, respectively, p < 0.05), and changes in the PHQ-2 had the strongest correlation to factor 3 (r = 0.24, p < 0.05). Abnormal QOD-NS scores at baseline were associated with effect size increases of 50% to 100% (p < 0.05).ConclusionThe QOD-NS measures 4 distinct factors. Eating-related questions had the greatest improvement after ESS. Health utility and CRS-specific QOL improvement most strongly associated with factor 2, while PHQ-2 changes are most highly associated with factor 3, suggesting a differential impact of the factors of the QOD-NS on varying aspects of QOL.
| S-EPMC6035764 | biostudies-literature