Tight Junctions, the Key Factor in Virus-Related Disease

Ding, Guofei; Shao, Qingyuan; Yu, Huan; Liu, Jiaqi; Li, Yingchao; Wang, Bin; Sang, Haotian; Li, Dexin; Bing, Aiying; Hou, Yanmeng; Xiao, Yihong

doi:10.3390/pathogens11101200

Cited by 11 publications

(11 citation statements)

References 101 publications

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“…Histological examination revealed that apical SARS-CoV-2 inoculation (upper Transwell inoculation) triggers epithelial layer degeneration and live viruses emerged in the lower Transwell chamber, indicating that intercellular proteins junctions are damaged and no longer act as a barrier. Furthermore, there are numerous pieces of evidence that SARS-CoV-2 infection disrupts tight junctions by metallopeptidases in the intestinal epithelium and Caco-2 monolayer[2,24,46,47] crossing the intestinal epithelial barriers by paracellular trafficking, as previously reported with other viruses[48–50]. It is also worth noting that the cellular receptor for SARS-CoV, angiotensin-converting enzyme 2 (ACE2), is located on the apical plasma membrane of polarized epithelial cells and mediates infection from the apical side of these cells[51].…”

Section: Discussionmentioning

confidence: 75%

Preferential apical infection of intestinal cell monolayers by SARS-CoV-2 is associated with damage to cellular barrier integrity: Implications for the physiopathology of COVID-19

Garrec,

Arrindell,

Andrieu

et al. 2024

Preprint

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SARS-CoV-2 can infect different organs, including the intestine. In Caco-2 intestinal cell line, SARS-CoV-2 modulates the ACE2 receptor expression and affects the expression of molecules involved in intercellular junctions. To further explore the possibility that the intestinal epithelium serves as an alternative infection route for SARS-CoV-2, we used a model of polarised intestinal cell monolayers grown on the polycarbonate membrane of Transwell inserts, inoculated with the virus either in the upper or lower chamber of culture. In both polarised Caco-2 cell monolayers and co-culture Caco-2/HT29 cell monolayer, apical SARS-CoV-2 inoculation was found to be much more effective in establishing infection than basolateral inoculation. In addition, apical SARS-CoV-2 infection triggers monolayer degeneration, as shown by histological examination, measurement of trans-epithelial electronic resistance, and cell adhesion molecule expression. During this process, the infectious viruses reach the lower chamber, suggesting either a transcytosis mechanism from the apical side to the basolateral side of cells, a paracellular trafficking of the virus after damage to intercellular junctions in the epithelial barrier, or both. Taken together, these data highlight a preferential tropism of SARS-CoV-2 for the apical side of the human intestinal tract and suggests that infection via the intestinal lumen leads to a systemic infection.

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Section: Discussionmentioning

confidence: 75%

Preferential apical infection of intestinal cell monolayers by SARS-CoV-2 is associated with damage to cellular barrier integrity: Implications for the physiopathology of COVID-19

Garrec,

Arrindell,

Andrieu

et al. 2024

Preprint

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“…The function of tight junctions is challenged by a variety of factors, including toxins, pathogens, or inflammation and cancer, which can lead to a loss of barrier integrity and finally to tissue damage [ 46 , 47 , 48 , 49 ]. Both the loss and assembly of tight junctions are regulated by numerous signaling pathways that involve a great variety of molecules, including protein kinases, phosphatases, G-proteins, and the regulators of their expression at both mRNA and protein levels [ 50 , 51 ].…”

Section: Mirnas Evs and Physical Barriersmentioning

confidence: 99%

miRNAs as Predictors of Barrier Integrity

et al. 2023

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The human body has several barriers that protect its integrity and shield it from mechanical, chemical, and microbial harm. The various barriers include the skin, intestinal and respiratory epithelia, blood–brain barrier (BBB), and immune system. In the present review, the focus is on the physical barriers that are formed by cell layers. The barrier function is influenced by the molecular microenvironment of the cells forming the barriers. The integrity of the barrier cell layers is maintained by the intricate balance of protein expression that is partly regulated by microRNAs (miRNAs) both in the intracellular space and the extracellular microenvironment. The detection of changes in miRNA patterns has become a major focus of diagnostic, prognostic, and disease progression, as well as therapy-response, markers using a great variety of detection systems in recent years. In the present review, we highlight the importance of liquid biopsies in assessing barrier integrity and challenges in differential miRNA detection.

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“…SARS-CoV-2 entrance in the epithelium is favored when the integrity of tight junctions (TJ), which are formed between neighboring cells and regulate the passage of ions and other small solutes, is altered. During the analysis of TJs in lung epithelial cells, the virus was found to affect the integrity of lung epithelial cells [ 83 ]. Additionally, the blood-brain barrier can be disturbed by SARS-CoV-2 and lead to derangements of tight junction and adherens junction proteins [ 84 ].…”

Section: Implications Of Altered Molecular Processes In Long Covid Sy...mentioning

confidence: 99%

Long COVID: Molecular Mechanisms and Detection Techniques

Constantinescu-Bercu,

Lobiuc,

Căliman-Sturdza

et al. 2023

IJMS

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Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), has emerged as a significant health concern following the COVID-19 pandemic. Molecular mechanisms underlying the occurrence and progression of long COVID include viral persistence, immune dysregulation, endothelial dysfunction, and neurological involvement, and highlight the need for further research to develop targeted therapies for this condition. While a clearer picture of the clinical symptomatology is shaping, many molecular mechanisms are yet to be unraveled, given their complexity and high level of interaction with other metabolic pathways. This review summarizes some of the most important symptoms and associated molecular mechanisms that occur in long COVID, as well as the most relevant molecular techniques that can be used in understanding the viral pathogen, its affinity towards the host, and the possible outcomes of host-pathogen interaction.

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Tight Junctions, the Key Factor in Virus-Related Disease

Cited by 11 publications

References 101 publications

Preferential apical infection of intestinal cell monolayers by SARS-CoV-2 is associated with damage to cellular barrier integrity: Implications for the physiopathology of COVID-19

Preferential apical infection of intestinal cell monolayers by SARS-CoV-2 is associated with damage to cellular barrier integrity: Implications for the physiopathology of COVID-19

miRNAs as Predictors of Barrier Integrity

Long COVID: Molecular Mechanisms and Detection Techniques

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