Lung Epithelial Cells from Obese Patients Have Impaired Control of SARS-CoV-2 Infection

被引:1
|
作者
Gaudet, Mellissa [1 ]
Kaufmann, Eva [1 ,2 ]
Jalaleddine, Nour [3 ]
Mogas, Andrea [1 ]
Hachim, Mahmood [3 ]
Senok, Abiola [3 ]
Divangahi, Maziar [1 ]
Hamid, Qutayba [1 ,4 ]
Al Heialy, Saba [1 ,3 ]
机构
[1] McGill Univ, Meakins Christie Labs, Res Inst, Hlth Ctr, Montreal, PQ H4A 3J1, Canada
[2] Queens Univ, Dept Biomed & Mol Sci, Kingston, ON K7L 3N6, Canada
[3] Mohammed Bin Rashid Univ Med & Hlth Sci, Coll Med, POB 505055, Dubai, U Arab Emirates
[4] Univ Sharjah, Sharjah Inst Med Res, POB 27272, Sharjah, U Arab Emirates
关键词
SARS-CoV-2; infection; obesity; immune response; ACE2; transcriptome profiling; bronchial epithelial cells; I INTERFERON; EXPRESSION; REPLICATION; MECHANISMS; RESPONSES;
D O I
10.3390/ijms24076729
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Obesity is known to increase the complications of the COVID-19 coronavirus disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the exact mechanisms of SARS-CoV-2 infection in obese patients have not been clearly elucidated. This study aims to better understand the effect of obesity on the course of SARS-CoV-2 infection and identify candidate molecular pathways involved in the progression of the disease, using an in vitro live infection model and RNA sequencing. Results from this study revealed the enhancement of viral load and replication in bronchial epithelial cells (NHBE) from obese subjects at 24 h of infection (MOI = 0.5) as compared to non-obese subjects. Transcriptomic profiling via RNA-Seq highlighted the enrichment of lipid metabolism-related pathways along with LPIN2, an inflammasome regulator, as a unique differentially expressed gene (DEG) in infected bronchial epithelial cells from obese subjects. Such findings correlated with altered cytokine and angiotensin-converting enzyme-2 (ACE2) expression during infection of bronchial cells. These findings provide a novel insight on the molecular interplay between obesity and SARS-CoV-2 infection. In conclusion, this study demonstrates the increased SARS-CoV-2 infection of bronchial epithelial cells from obese subjects and highlights the impaired immunity which may explain the increased severity among obese COVID-19 patients.
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页数:14
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