Co-Expression of Mitochondrial Genes and ACE2 in Cornea Involved in COVID-19.
Invest Ophthalmol Vis Sci
; 61(12): 13, 2020 10 01.
Article
em En
| MEDLINE
| ID: mdl-33049061
ABSTRACT
Purpose:
The coronavirus disease 2019 (COVID-19) pandemic severely challenges public health and necessitates the need for increasing our understanding of COVID-19 pathogenesis, especially host factors facilitating virus infection and propagation. The aim of this study was to investigate key factors for cellular susceptibility to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection in the ocular surface cells.Methods:
We combined co-expression and SARS-CoV-2 interactome network to predict key genes at COVID-19 in ocular infection based on the premise that genes underlying a disease are often functionally related and functionally related genes are often co-expressed.Results:
The co-expression network was constructed by mapping the well-known angiotensin converting enzyme (ACE2), TMPRSS2, and host susceptibility genes implicated in COVID-19 genomewide association study (GWAS) onto a cornea, retinal pigment epithelium, and lung. We found a significant co-expression module of these genes in the cornea, revealing that cornea is potential extra-respiratory entry portal of SARS-CoV-2. Strikingly, both co-expression and interaction networks show a significant enrichment in mitochondrial function, which are the hub of cellular oxidative homeostasis, inflammation, and innate immune response. We identified a corneal mitochondrial susceptibility module (CMSM) of 14 mitochondrial genes by integrating ACE2 co-expression cluster and SARS-CoV-2 interactome. The gene ECSIT, as a cytosolic adaptor protein involved in inflammatory responses, exhibits the strongest correlation with ACE2 in CMSM, which has shown to be an important risk factor for SARS-CoV-2 infection and prognosis.Conclusions:
Our co-expression and protein interaction network analysis uncover that the mitochondrial function related genes in cornea contribute to the dissection of COVID-19 susceptibility and potential therapeutic interventions.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pneumonia Viral
/
RNA
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Regulação da Expressão Gênica
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Infecções por Coronavirus
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Peptidil Dipeptidase A
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Córnea
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Genes Mitocondriais
/
Betacoronavirus
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article