Co-Expression of Mitochondrial Genes and ACE2 in Cornea Involved in COVID-19.
Invest Ophthalmol Vis Sci
; 61(12): 13, 2020 10 01.
Article
in English
| MEDLINE | ID: covidwho-852836
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pneumonia, Viral
/
RNA
/
Gene Expression Regulation
/
Coronavirus Infections
/
Peptidyl-Dipeptidase A
/
Cornea
/
Genes, Mitochondrial
/
Betacoronavirus
Type of study:
Observational study
/
Prognostic study
Limits:
Humans
Language:
English
Journal:
Invest Ophthalmol Vis Sci
Year:
2020
Document Type:
Article
Affiliation country:
Iovs.61.12.13
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