Biomechanism Of How Ebola Attaches To Host Cells Discovered
According to recent reports, there is a drastic increase in the number of Ebola cases in the Democratic Republic of Congo which makes it the second-worst outbreak in history following the 2014 outbreak in West Africa where 29,000 people were infected and more than 11,000 died.
This latest milestone is an urgent reminder of the need to develop effective prevention and treatment agents for this often deadly disease.
The people who are infected with the Ebola virus experience severe illness, including hemorrhagic fever, which may lead to internal bleeding. According to the U.S. Centers for Disease Control and Prevention, there is no specific medical treatment for Ebola until today.
The main aim of developing treatments for the disease is understanding the mechanisms of the infection process. Researchers know that to enter a human cell, Ebola takes advantage of a natural process called macropinocytosis, through which it cleans up its environment by internalizing the dead cell debris that surrounds it. Proteins on a cell’s surface to serve as receptors allowing immune cells to comprehend the dead cell debris and internalize it. The virus interacts with T-cell immunoglobulin proteins and mucin domain (TIM) proteins and uses them to hijack its way into the cella and Once inside, the Ebola virus membrane fuses to the endosome, which has formed around it and releases its genetic content into the cell.
Frank Zhang, associate professor of bioengineering and of mechanical engineering at Lehigh University said that the Viral RNA of Ebola further hijacks the cell mechanism to create proteins and replicate themselves inside. Then it nicks off the membrane leading to the formation of a new virus – while the healthy host cell dies.
Anand Jagota CEO and founder of the Lehigh’s Department of Bioengineering and Professor of Chemical and Biomolecular Engineering stated that- While Ebola-host cell attachment has been shown to depend on the molecular biomechanics of interaction between receptors on the cell surface and the outer coating of the virus, the quantitative understanding essential for guiding the development of treatments has not been developed yet.
The Scientists Zhang and Jagota have teamed up in order to understand the biomechanics of Ebola virus-host cell adhesion. The project comprises of Jagota’s experience in computational molecular adhesion mechanics with Zhang’s focus in mechanosensing, or how cells sense and respond to mechanical stimuli. The duo working along with their co-team members Sven Moller-Tank and Wendy Maury in the University of Iowa have developed a simple model that characterizes the biomechanics of Ebola virus-host cell adhesion? findings that could provide new and helpful information regarding the path to creating an effective Ebola treatment. Their research has been published in Scientific Reports in an article titled: “Biomechanical characterization of TIM protein-mediated Ebola virus-host cell adhesion”.
Zhang stated that- they utilized single-molecule force spectroscopy to measure the specific interaction forces between the TIM proteins of a host cell and Ebola-virus-like particles.
It is important for Ebola attachment into a host cell in addition to illuminating the biomechanical parameters, the group also demonstrated experimentally that TIM-Ebola virus connections are mechanically comparable to adhesion molecules (e.g., selectin) ligand interactions. Through a simple mechanical model, the team further demonstrate how molecular binding parameters to determine if they’re sufficient for viral adhesion.
The main idea behind this model is to show how single-molecule measurements can be combined with other physical properties of the system, such as density of ligand-receptor pairs and membrane stiffness in order to predict whether and to what extent a viral particle will adhere to the cell membrane. The team models attachment as being pushed by adhesion involving TIM proteins and phosphatidylserine on the surface of the virus thought to mediate the virus-host cell attachment and resisted by tissue bending.
Jagota said, “The model’s simplicity has enabled us to highlight the importance of two dimensionless groups of parameters and their possible ability to block adhesion,”.
For instance, in the study, Zhang would bring a virus-like particle to a cell with its TIM receptor expressed, observe their interaction, and pull them apart to ascertain the mechanical strength of their interaction, or how much force is required to pull them apart.
To understand the interaction between Ebola and the cell mathematical models were used by Jagota which included what amount of attributes represent the Ebola virus, what is its stiffness, its form, what properties represent the cell and the components it presents on its surface.
Jagota concluded that – The expectation is that this quantitative knowledge about the biomechanics of adhesion may be used to predict conditions for Ebola’s attachment,” Long-term, the goal is for this information to help bring about new pharmacological targets and help in the development of much-needed antiviral therapeutics for the treatment and prevention of Ebola.