International Journal of Molecular Medical Science, 2024, Vol.14, No.2, 100-105 http://medscipublisher.com/index.php/ijmms 100 Scientific Commentary Open Access Innate Defense Role of Extracellular Vesicles: The Critical Role of Phosphatidylserine in Combating Apoptotic Mimicry Viruses ManmanLi Hainan Institute of Tropical Agricultural Resources, Sanya, 572024, Hainan, China Corresponding email: lmm314.editor@gmail.com International Journal of Molecular Medical Science, 2024, Vol.14, No.2 doi: 10.5376/ijmms.2024.14.0013 Received: 27 Mar., 2024 Accepted: 18 Apr., 2024 Published: 29 Apr., 2024 Copyright © 2024 Li, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Li M.M., 2024, Innate defense role of extracellular vesicles: the critical role of phosphatidylserine in combating apoptotic mimicry viruses, International Journal of Molecular Medical Science, 14(2): 100-105 (doi: 10.5376/ijmms.2024.14.0013) The paper titled "Phosphatidylserine-exposing extracellular vesicles in body fluids are an innate defence against apoptotic mimicry viral pathogens" was published in the journal "Nature Microbiology" on March 25, 2024. Authored by Rüdiger Groß, Hanna Reßin, and Janis A. Müller, the research was conducted at the Institute of Molecular Virology at the University Medical Center Ulm, Germany, and the Institute of Virology at Philipps University of Marburg, Germany. The study reveals that extracellular vesicles (EVs) in body fluids combat viral infections by exposing phosphatidylserine (PS), which disrupts viral attachment and entry, thus serving an antiviral function. The results indicate that these EVs can effectively inhibit several viruses, including Dengue, West Nile, Chikungunya, Ebola, and Vesicular stomatitis viruses. However, they show lower inhibitory effects on SARS-CoV-2, HIV-1, Hepatitis C, and Herpes viruses due to these pathogens utilizing different receptor mechanisms for cell infection. 1 Interpretation of Experimental Data Researchers collected critical data through lipidomic analysis, flow cytometry, and viral infection experiments. The experimental data indicate that the exposure of phosphatidylserine is crucial to the antiviral properties of extracellular vesicles (EVs). Additionally, the study shows that liposomes containing synthetically produced phosphatidylserine can also inhibit viral infections. Figure 1 illustrates the role of phosphatidylserine (PS) in Zika virus (ZIKV) and other viral infections. Panel a shows the process where phosphatidylserine decarboxylase (PSD) converts PS in the viral envelope into phosphatidylethanolamine (PE). Panel b indicates that after PSD treatment, the infection rates of ZIKV, HIV-1, HSV-1, and HSV-2 significantly decrease. Panels c and d explore the effects of liposomes with different PS contents on inhibiting ZIKV infection, revealing that the inhibitory effect on infection significantly increases with higher PS content. The data reveal the crucial role of PS in the viral infection process, establishing it as a potential antiviral target. Figure 2 investigates the effects of liposomes containing phosphatidylserine (PS) in inhibiting Zika virus (ZIKV) infection. Panel a shows that adding PS liposomes either prior to or simultaneously with the virus significantly inhibits ZIKV infection. Panel b demonstrates that PS liposomes exhibit a concentration-dependent inhibitory effect across different viral inoculation doses (MOI). Panel c indicates that individual headgroup small molecules do not possess significant antiviral activity. Panels d and e reveal that liposomes with a higher PS content have stronger antiviral effects. Panels f and g, using fluorescence quantification, show that PS liposomes can reduce viral attachment and increase the attachment of the liposomes themselves. Panel h, through fluorescence microscopy images, visually displays the competitive inhibitory effect of the liposomes on the virus. Figure 3 explores the levels and characteristics of phosphatidylserine (PS) in extracellular vesicles (EVs) across different body fluids. Panel a describes the workflow for purifying EVs using Tangential Flow Filtration (TFF) and BE-SEC. Panel b confirms the enrichment of characteristic EV proteins in different samples through Western
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