For the first time, a system has been developed to let researchers watch the Ebola virus through a microscope as it infects human cells in real-time. The discovery, published in mBio, the online journal of American Society for Microbiology, helps the identification of the processes behind the fusion of the virus with the host cell. Through this system, a series of Ebola-like virus particles are watched via microscope as they fuse with the human cells. Eventually, these findings may reveal key viral proteins and their interaction with human cells that could pave the road for future Ebola vaccines or drugs development.
The newly discovered real-time system may help researchers find a cure for Ebola
The Ebola epidemic that hit Western Africa in 2014-2015 caused over 11,000 deaths, wrecking down the otherwise unprepared and underdeveloped health care system. Although the current epidemic has been finally contained, there’s no way to anticipate where or when the next outbreak may occur. The need for a preventive treatment to restrain the next plague surge is of paramount importance, and specific drugs to treat infected patients must be developed as soon as possible. The system developed by the research team at the Albert Einstein College of Medicine in Bronx, New York led by Dr. Kartik Chandran, associate professor of microbiology and immunology, may provide critical knowledge that could be used to fight off this deadly disease’s next outbreak.
The virus enters inside the host’s cells by “convincing” them to engulf (phagocytize) it. When it’s brought to the endosome, the cell’s organelle that recycles internal or external biologic material, it starts its infiltration. The Ebola virus is, in fact, able to subvert normal endosomal pathways, and instead of being broken down into simpler proteic material, it spreads the infection by making multiple copies of itself. Thanks to his envelope, the virus is protected from endosomal breaking activity as well as being able to bind to the endosomal membrane in order to release his genes inside the cell itself.
Scientists discover the first steps of Ebola infection. Is a new Ebola vaccine now a possibility?
The research team engineered a particular Ebola-like virus with a peculiar membrane that is coloured with a fluorescent dye. As soon as the viral membrane fuses itself with the cellular membrane, the dye is lit up, allowing the scientists to observe the infiltration process closely through microscope lenses. This one step of the viral infection spread is one of the richest in potential targets for antiviral treatments such as medications and vaccines, as Chandran explained. Researchers discovered how the ZMappTM antibody cocktail used to contain the last Ebola epidemic targets the NPC1, a specific cellular protein that binds to the Ebola glycoprotein when the fusion occurs. They also pinpointed the exact cellular compartment responsible for the viral fusion and understood how this process’ next stage requires cathepsin proteases, a series of additional proteins, to be completed.
Many more cellular factors are probably involved, as just a small fraction (about 10%) of the viral particles deployed by the Ebola virus initiate fusion. Chandran’s team is working on rebuilding the whole Ebola infection process to understand all the steps required by the virus to release the viral RNA genome into the host. Identifying further vulnerable steps of this process may, in fact, help scientists develop new effective Ebola vaccines and treatment drugs to block future infections and epidemics.
Article by Dr. Claudio Butticè, PharmD.
- Jennifer S. Spence, Tyler B. Krause, Eva Mittler, Rohit K. Jangra, Kartik Chandran. Direct Visualization of Ebola Virus Fusion Triggering in the Endocytic Pathway. mBio, 2016; 7 (1): e01857-15 DOI:10.1128/mBio.01857-15
- American Society for Microbiology. “Real-time Ebola fusion system yields clues to stopping infection.” ScienceDaily. ScienceDaily, 11 February 2016