Membrane Rafts: Portals for Viral Entry

Ripa, Inés; Andreu, Sabina; Löpez‐Guerrero, José Antonio; Bello-Morales, Raquel

doi:10.3389/fmicb.2021.631274

Cited by 85 publications

(80 citation statements)

References 274 publications

(138 reference statements)

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“…Blocking the priming or the proteolytic cleavage are possible targets for early drug interventions (Hoffmann et al, 2020b). Recent studies on the host cell membrane and viral interactions have brought novel insights into the role of cellular lipids in the process of viral entry (Carpinteiro et al, 2020;Ripa et al, 2021). Particularly, sphingolipids have been shown to affect cell entry of bacteria and of different viruses (Schneider-Schaulies and Schneider-Schaulies, 2015;Simonis and Schubert-Unkmeir, 2018).…”

Section: Introductionmentioning

confidence: 99%

Sphingolipids as Modulators of SARS-CoV-2 Infection

Törnquist

Asghar

Srinivasan

et al. 2021

Front. Cell Dev. Biol.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the COVID-19 pandemic with severe consequences for afflicted individuals and the society as a whole. The biology and infectivity of the virus has been intensively studied in order to gain a better understanding of the molecular basis of virus-host cell interactions during infection. It is known that SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) via its spike protein. Priming of the virus by specific proteases leads to viral entry via endocytosis and to the subsequent steps in the life cycle of SARS-CoV-2. Sphingosine and ceramide belong to the sphingolipid family and are abundantly present in cell membranes. These lipids were recently shown to interfere with the uptake of virus particles of SARS-CoV-2 into epithelial cell lines and primary human nasal cells in culture. The mechanisms of action were partly different, as sphingosine blocked, whilst ceramide facilitated viral entry. Acid sphingomyelinase (ASM) is vital for the generation of ceramide and functional inhibition of ASM by drugs like amitriptyline reduced SARS-CoV-2 entry into the epithelial cells. Recent data indicates that serum level of sphingosine-1-phosphate (S1P) is a prognostic factor for COVID-2 severity. Further, stimulation of sphingosine-1-phosphate receptor 1 (S1PR1) might also constrain the hyper-inflammatory conditions linked to SARS-CoV-2. Here, we review recent exciting findings regarding sphingolipids in the uptake of SARS-CoV-2 and in the course of COVID-19 disease. More studies are required on the mechanisms of action and the potential use of antidepressant drugs and sphingolipid modifiers in SARS-CoV-2 infections and in the treatment of the more serious and fatal consequences of the disease.

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Section: Introductionmentioning

confidence: 99%

Sphingolipids as Modulators of SARS-CoV-2 Infection

Törnquist

Asghar

Srinivasan

et al. 2021

Front. Cell Dev. Biol.

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“…entry) and later stages of replication (i.e. assembly and budding) [11]. Due to the integral role lipids play in viral replication, drugs that target lipid metabolism are promising anti-viral treatments [10,12].…”

Section: Lipids Are Critical To Viral Replicationmentioning

confidence: 99%

How lipidomics can transform our understanding of virus infections

Kyle

2021

Expert Review of Proteomics

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Section: Internalization Of Rvar2 Is Cell Energy-dependent and Can Occur Via Different Endocytic Pathwaysmentioning

confidence: 99%

“…Endocytic pathways can be classified into three classes: (i) Endocytic pathways that take place in lipid rafts, which include the majority of clathrin-independent endocytic pathways such as caveolae-mediated endocytosis 24,25 . (ii) pathways that do not involve lipid rafts in the endocytic vesicle, namely clathrin-mediated endocytosis (CME) 2,24 . (iii) Endocytic pathways for which the endocytic vesicle can contain lipid rafts together with non-raft membrane domains, and these include phagocytosis and micropinocytosis 24,26 .…”

Section: Internalization Of Rvar2 Is Cell Energy-dependent and Can Occur Via Different Endocytic Pathwaysmentioning

confidence: 99%

“…(ii) pathways that do not involve lipid rafts in the endocytic vesicle, namely clathrin-mediated endocytosis (CME) 2,24 . (iii) Endocytic pathways for which the endocytic vesicle can contain lipid rafts together with non-raft membrane domains, and these include phagocytosis and micropinocytosis 24,26 . Amongst the many endocytic mechanism cells can use to internalize external materials, two major routes are clathrin-mediated and caveolaemediated endocytosis (CavME) 1 .…”

Section: Internalization Of Rvar2 Is Cell Energy-dependent and Can Occur Via Different Endocytic Pathwaysmentioning

confidence: 99%

See 1 more Smart Citation

Internalization and Trafficking of CSPG-Bound Recombinant VAR2CSA Lectins in Cancer Cells

Wang

Nelepcu

Hui

et al. 2021

Preprint

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Proteoglycans are proteins that are modified with glycosaminoglycan chains. Chondroitin sulfate proteoglycans (CSPGs) are currently being exploited as targets for drug-delivery in various cancer indications, however basic knowledge on how CSPGs are internalized in tumor cells is lacking. In this study we took advantage of a recombinant CSPG-binding lectin VAR2CSA (rVAR2) to track internalization and cell fate of CSPGs in tumor cells. We found that rVAR2 is internalized into cancer cells via multiple internalization mechanisms after initial docking on cell surface CSPGs. Regardless of the internalization pathway used, CSPG-bound rVAR2 was trafficked to the early endosomes in an energy-dependent manner but not further transported to the lysosomal compartment. Instead, internalized CSPG-bound rVAR2 proteins were secreted with exosomes to the extracellular environment in a strictly chondroitin sulfate-dependent manner. In summary, our work describes the cell fate of rVAR2 proteins in tumor cells after initial binding to CSPGs, which can be further used to inform development of rVAR2-drug conjugates and other therapeutics targeting CSPGs.

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Membrane Rafts: Portals for Viral Entry

Cited by 85 publications

References 274 publications

Sphingolipids as Modulators of SARS-CoV-2 Infection

Sphingolipids as Modulators of SARS-CoV-2 Infection

How lipidomics can transform our understanding of virus infections

Internalization and Trafficking of CSPG-Bound Recombinant VAR2CSA Lectins in Cancer Cells

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