Breakthrough study on how Marburg and Ebola viruses interact with cell membranes

Medical-News: Researchers from the Laboratory of Membrane and Ion Channel Modeling at the Institute of Cytology of the Russian Academy of Sciences have uncovered fascinating details about how Marburg and Ebola viruses interact with cell membranes. By studying fragments of these viruses' fusion peptides, the research aims to shed light on the specific ways they infect host cells and, more importantly, how this process can be inhibited. This Medical News report will explore these findings and how they can pave the way for potential antiviral treatments.


Breakthrough study on how Marburg and Ebola viruses interact with cell membranes

Understanding the Fusion Process
The Marburg and Ebola viruses are part of the filovirus family, which causes severe hemorrhagic fevers with a mortality rate as high as 90%. Their infection process starts when the viral particle binds to the host cell's membrane, initiating a fusion process between the viral and cellular membranes. This fusion allows the virus to inject its genetic material into the host cell, starting the infection.

The fusion process is mediated by specific proteins on the virus's surface, called fusion peptides. These peptides are small sequences of amino acids that play a critical role in the merging of viral and cell membranes. In this study, scientists used various techniques, including fluorescence assays and electron microscopy, to analyze how fragments of Marburg and Ebola fusion peptides interact with lipid membranes.
 
The Role of Lipid Membranes
The study focused on the interaction of these viral peptides with lipid membranes, specifically liposomes - tiny spherical vesicles made from lipids, which mimic cell membranes. Different lipid compositions were tested to observe how they influence the fusion process. This is important because understanding which lipids enhance or inhibit membrane fusion could lead to targeted antiviral therapies.
 
The researchers observed that the Marburg virus fusion peptide (FPMARV) and the Ebola virus fusion peptide (FPEBOV) induced varying levels of membrane fusion based on the lipid composition of the vesicles. The Marburg fusion peptide demonstrated significant fusogenic activity, reaching about 85% fusion in certain lipid environments, while the Ebola peptide induced approximately 60% fusion under similar conditions.
 
Inhibition by Plant Compounds
One of the key findings of this study is the potential for plant polyphenols, such as quercetin and myricetin, to inhibit the membrane fusion process. These compounds are naturally occurring in many plants and have been studied for their antiviral properties. The researchers found that when these polyphenols were added to the system, they were able to significantly inhibit the fusion of liposomes induced by the Marburg fusion peptide. Quercetin and myricetin were shown to prevent vesicle fusion by approximately 30-40%, highlighting their potential as antiviral agents.
 
Interestingly, other compounds like fisetin and piperine d id not show the same inhibitory effects. The inhibition of the fusion process by quercetin and myricetin suggests that these compounds could counteract the dehydration of lipid bilayers, which is critical for fusion to occur. This study demonstrates the potential of using small, hydrophilic molecules to inhibit viral entry into host cells.
 
Detailed Mechanism of Fusion
The study delved into the specifics of how fusion peptides from Marburg and Ebola viruses alter the physical properties of lipid membranes. The researchers observed that the Marburg fusion peptide prefers lipid environments with certain structural characteristics, such as those that promote negative curvature in the membrane. This curvature stress helps initiate membrane fusion, a crucial step for the virus to infect cells.
 
When the lipid composition was altered to include different lipid species, such as phosphatidylethanolamine (PE) or ceramide, the ability of the viral peptides to induce membrane fusion changed. For instance, adding PE to the membrane reduced the fusogenic activity of the Marburg peptide by about five times, indicating that this lipid might inhibit viral fusion. On the other hand, replacing sphingomyelin (SM) with ceramide slightly enhanced the fusion activity of the Ebola peptide, which is consistent with previous studies showing that viral infections increase ceramide production in host cells.
 
Importance of Lipid Hydration and Membrane Packing
Another interesting aspect of the study was the role of membrane hydration in the fusion process. The researchers proposed that the Marburg fusion peptide facilitates membrane fusion by dehydrating the lipid bilayer, reducing the distance between the two membranes and allowing them to merge. This dehydration-driven fusion mechanism was confirmed by analyzing how the peptides affected the thermotropic behavior of lipids, revealing that certain lipid environments made the membranes more susceptible to fusion.
 
The study also found that the length of the lipid tails influenced how the fusion peptides interacted with the membranes. Shorter lipid tails promoted the formation of lipid tail protrusions, which destabilize the membrane and make fusion more likely. This observation adds another layer of complexity to understanding how viruses manipulate the host cell membrane to initiate infection.
 
Conclusions
This study represents a significant advancement in our understanding of how Marburg and Ebola viruses initiate infection by fusing with host cell membranes. The key findings include the identification of lipid environments that either promote or inhibit viral membrane fusion, as well as the discovery that plant polyphenols like quercetin and myricetin can act as potent inhibitors of this process.
 
The results also suggest that membrane hydration and lipid packing play a critical role in the fusogenic activity of viral peptides, providing new avenues for antiviral drug development. By targeting the specific lipid environments and membrane properties that facilitate viral fusion, it may be possible to develop therapies that prevent these deadly viruses from infecting human cells.
 
As the search for antiviral treatments continues, this study opens the door to new strategies that focus on lipid-mediated inhibition of viral fusion. The use of naturally occurring compounds, such as quercetin and myricetin, offers a promising and accessible approach to combating viral infections like Marburg and Ebola.
 
The study findings were published in the peer-reviewed International Journal of Molecular Sciences.
https://www.mdpi.com/1422-0067/25/18/9901
 
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