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1.
Arch Virol ; 166(1): 271-274, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1384460

ABSTRACT

Viral RNAs can perturb the miRNA regulatory network, competing with host RNAs as part of their infective process. An in silico competing endogenous RNA (ceRNA) analysis has been carried on SARS-CoV-2. The results suggest that, in humans, the decrease of microRNA activity caused by viral RNAs can lead to a perturbation of vesicle trafficking and the inflammatory response, in particular by enhancing KLF10 activity. The results suggest also that, during the study of the mechanics of viral infections, it could be of general interest to investigate the competition of viral RNA with cellular transcripts for shared microRNAs.


Subject(s)
Gene Regulatory Networks/genetics , RNA, Messenger/genetics , RNA, Viral/genetics , SARS-CoV-2/genetics , A549 Cells , COVID-19/pathology , Cell Line, Tumor , Early Growth Response Transcription Factors/genetics , Early Growth Response Transcription Factors/metabolism , Humans , Kruppel-Like Transcription Factors/genetics , Kruppel-Like Transcription Factors/metabolism , MicroRNAs/genetics
3.
Front Immunol ; 12: 648815, 2021.
Article in English | MEDLINE | ID: covidwho-1325521

ABSTRACT

Multiple lines of evidence have demonstrated that cigarette smoke or Chronic Obstructive Pulmonary Disease upregulates angiotensin-converting enzyme 2, the cellular receptor for the entry of the severe acute respiratory syndrome coronavirus 2, which predisposes individuals to develop severe Coronavirus disease 2019. The reason for this observation is unknown. We recently reported that the loss of function of Miz1 in the lung epithelium in mice leads to a spontaneous COPD-like phenotype, associated with upregulation of angiotensin-converting enzyme 2. We also reported that cigarette smoke exposure downregulates Miz1 in lung epithelial cells and in mice, and Miz1 is also downregulated in the lungs of COPD patients. Here, we provide further evidence that Miz1 directly binds to and represses the promoter of angiotensin-converting enzyme 2 in mouse and human lung epithelial cells. Our data provide a potential molecular mechanism for the upregulation of angiotensin-converting enzyme 2 observed in smokers and COPD patients, with implication in severe Coronavirus disease 2019.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , Kruppel-Like Transcription Factors/metabolism , Receptors, Virus/genetics , Transcription, Genetic , Alveolar Epithelial Cells/metabolism , Angiotensin-Converting Enzyme 2/metabolism , Animals , BTB-POZ Domain , Cell Line , Cigarette Smoking/adverse effects , Kruppel-Like Transcription Factors/chemistry , Kruppel-Like Transcription Factors/genetics , Mice , Promoter Regions, Genetic , Protein Binding , Receptors, Virus/metabolism , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/metabolism , Transcription, Genetic/drug effects , Tumor Necrosis Factors/pharmacology , Virus Internalization
4.
Arch Virol ; 166(1): 271-274, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-928484

ABSTRACT

Viral RNAs can perturb the miRNA regulatory network, competing with host RNAs as part of their infective process. An in silico competing endogenous RNA (ceRNA) analysis has been carried on SARS-CoV-2. The results suggest that, in humans, the decrease of microRNA activity caused by viral RNAs can lead to a perturbation of vesicle trafficking and the inflammatory response, in particular by enhancing KLF10 activity. The results suggest also that, during the study of the mechanics of viral infections, it could be of general interest to investigate the competition of viral RNA with cellular transcripts for shared microRNAs.


Subject(s)
Gene Regulatory Networks/genetics , RNA, Messenger/genetics , RNA, Viral/genetics , SARS-CoV-2/genetics , A549 Cells , COVID-19/pathology , Cell Line, Tumor , Early Growth Response Transcription Factors/genetics , Early Growth Response Transcription Factors/metabolism , Humans , Kruppel-Like Transcription Factors/genetics , Kruppel-Like Transcription Factors/metabolism , MicroRNAs/genetics
5.
Sci Adv ; 6(33): eabb7238, 2020 08.
Article in English | MEDLINE | ID: covidwho-733188

ABSTRACT

Cigarette smoking, the leading cause of chronic obstructive pulmonary disease (COPD), has been implicated as a risk factor for severe disease in patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we show that mice with lung epithelial cell-specific loss of function of Miz1, which we identified as a negative regulator of nuclear factor κB (NF-κB) signaling, spontaneously develop progressive age-related changes resembling COPD. Furthermore, loss of Miz1 up-regulates the expression of Ace2, the receptor for SARS-CoV-2. Concomitant partial loss of NF-κB/RelA prevented the development of COPD-like phenotype in Miz1-deficient mice. Miz1 protein levels are reduced in the lungs from patients with COPD, and in the lungs of mice exposed to chronic cigarette smoke. Our data suggest that Miz1 down-regulation-induced sustained activation of NF-κB-dependent inflammation in the lung epithelium is sufficient to induce progressive lung and airway destruction that recapitulates features of COPD, with implications for COVID-19.


Subject(s)
Epithelial Cells/metabolism , Kruppel-Like Transcription Factors/metabolism , Lung/metabolism , Peptidyl-Dipeptidase A/metabolism , Phenotype , Protein Inhibitors of Activated STAT/genetics , Pulmonary Disease, Chronic Obstructive/genetics , Ubiquitin-Protein Ligases/genetics , Up-Regulation/genetics , Angiotensin-Converting Enzyme 2 , Animals , Betacoronavirus , COVID-19 , Coronavirus Infections/metabolism , Coronavirus Infections/virology , Gene Knockout Techniques , Humans , Mice , Mice, Inbred C57BL , Mice, Knockout , Pandemics , Pneumonia, Viral/metabolism , Pneumonia, Viral/virology , Protein Inhibitors of Activated STAT/metabolism , Pulmonary Disease, Chronic Obstructive/etiology , Pulmonary Disease, Chronic Obstructive/metabolism , SARS-CoV-2 , Signal Transduction/genetics , Smoking/adverse effects , Transcription Factor RelA/metabolism , Ubiquitin-Protein Ligases/metabolism
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