Computationally predicted SARS-COV-2 encoded microRNAs target NFKB, JAK/STAT and TGFB signaling pathways

Lecarpentier²,

2021

Front. Immunol.

The Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), has quickly reached pandemic proportions. Cytokine profiles observed in COVID-19 patients have revealed increased levels of IL-1β, IL-2, IL-6, and TNF-α and increased NF-κB pathway activity. Recent evidence has shown that the upregulation of the WNT/β-catenin pathway is associated with inflammation, resulting in a cytokine storm in ARDS (acute respire distress syndrome) and especially in COVID-19 patients. Several studies have shown that the WNT/β-catenin pathway interacts with PPARγ in an opposing interplay in numerous diseases. Furthermore, recent studies have highlighted the interesting role of PPARγ agonists as modulators of inflammatory and immunomodulatory drugs through the targeting of the cytokine storm in COVID-19 patients. SARS-CoV2 infection presents a decrease in the angiotensin-converting enzyme 2 (ACE2) associated with the upregulation of the WNT/β-catenin pathway. SARS-Cov2 may invade human organs besides the lungs through the expression of ACE2. Evidence has highlighted the fact that PPARγ agonists can increase ACE2 expression, suggesting a possible role for PPARγ agonists in the treatment of COVID-19. This review therefore focuses on the opposing interplay between the canonical WNT/β-catenin pathway and PPARγ in SARS-CoV2 infection and the potential beneficial role of PPARγ agonists in this context.

Section: Wnt/b-catenin Pathway and Sars-cov-2 Infectionmentioning

confidence: 99%

Interplay of Opposing Effects of the WNT/β-Catenin Pathway and PPARγ and Implications for SARS-CoV2 Treatment

Lecarpentier²,

2021

Front. Immunol.

American Journal of Physiology-Lung Cellular and Molecular Phys

“…In addition to MRE/GRE and SP1-binding sites, the Na,K-ATPase β 1 -subunit contains prostaglandin-, hypoxia-, thyroid-, calcium-, and serum-response elements ( 44 ). Of note, it has been previously demonstrated that both SARS-CoV and SARS-CoV-2 alter the activity of AP-1 ( 45 , 46 ) and SP1 transcriptional pathways ( 47 ). Moreover, two recent publications demonstrated that infection of various lung epithelial cells with SARS-CoV-2 leads to decreased expression of the α 1 -, α 2 -, α 3 -, β 1 -, and β 3 -subunits of the Na,K-ATPase at the transcriptional level ( 48 , 49 ).…”

Section: Direct Effects Of Sars-cov-2 Infection On Expression Maturation and Trafficking Of Nak-atpase In Infected Cellsmentioning

confidence: 99%

Molecular mechanisms of Na,K-ATPase dysregulation driving alveolar epithelial barrier failure in severe COVID-19

Kryvenko

Vadász

2021

A significant number of patients with coronavirus disease 2019 (COVID‑19) develop acute respiratory distress syndrome (ARDS) that is associated with a poor outcome. The molecular mechanisms driving failure of the alveolar barrier upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV‑2) infection remain incompletely understood. The Na,K‑ATPase is an adhesion molecule and a plasma membrane transporter that is critically required for proper alveolar epithelial function by both promoting barrier integrity and resolution of excess alveolar fluid, thus enabling appropriate gas exchange. However, numerous SARS-CoV‑2-mediated and COVID‑19-related signals directly or indirectly impair the function of the Na,K-ATPase, thereby potentially contributing to disease progression. In this Perspective, we highlight some of the putative mechanisms of SARS-CoV-2-driven dysfunction of the Na,K‑ATPase, focusing on expression, maturation and trafficking of the transporter. A therapeutic mean to selectively inhibit the maladaptive signals that impair the Na,K-ATPase upon SARS-CoV‑2 infection might be effective in reestablishing the alveolar epithelial barrier and promoting alveolar fluid clearance (AFC) and thus advantageous in patients with COVID‑19-associated ARDS.

“…This study further demonstrates that sv-RNA molecules derived from viral nucleoprotein and non-structural protein 3 regions contribute to SARS-CoV pathogenesis, which is reduced by antagonization of these sv-RNAs ( Morales et al, 2017 ). Another bioinformatics-driven prediction study revealed that SARS-CoV-2 encodes multiple putative rv-miRNAs from different regions of the viral genome and targets various signaling molecules involved in apoptosis, immune function, cell cycle, and transcription ( Aydemir et al, 2021 ). However, further investigations are required to experimentally evaluate their expression and biological functions in the context of viral infection.…”

Section: Rna Virus-encoded Mirnas (Rv-mirnas)mentioning

confidence: 99%

RNA Virus-Encoded miRNAs: Current Insights and Future Challenges

2021

MicroRNAs are small non-coding RNAs that regulate eukaryotic gene expression at the post-transcriptional level and affect a wide range of biological processes. Over the past two decades, numerous virus-encoded miRNAs have been identified. Some of them are crucial for viral replication, whereas others can help immune evasion. Recent sequencing-based bioinformatics methods have helped identify many novel miRNAs, which are encoded by RNA viruses. Unlike the well-characterized DNA virus-encoded miRNAs, the role of RNA virus-encoded miRNAs remains controversial. In this review, we first describe the current knowledge of miRNAs encoded by various RNA viruses, including newly emerging viruses. Next, we discuss how RNA virus-encoded miRNAs might facilitate viral replication, immunoevasion, and persistence in their hosts. Last, we briefly discuss the challenges in the experimental methodologies and potential applications of miRNAs for diagnosis and therapeutics.