Australian scientists recently revealed for the first time how the rabies virus successfully "hijacks" human cells. This breakthrough is expected to pave the way for the development of new antiviral drugs and vaccines. The research team, led by Monash University and the University of Melbourne, published a paper in Nature Communications stating that although rabies virus only produces a very small number of proteins, it can regulate many key activities within cells.
Experts believe that the same mechanism may also be exploited by high-risk viruses such as Nipah virus and Ebola virus. If confirmed, it will make it possible to develop drugs that block common virus strategies.
Images of human cells under a confocal microscope show that the rabies virus P3 protein (green) forms a droplet-like structure in the cell nucleus (blue), is located in the nucleolus, and combines with the cell's structural framework-microtubules (red) to form a bundle-like structure. Image source: Stephen Rawlinson, Monash University
Associate Professor Mosley, head of the Viral Pathogenesis Laboratory at the Monash Biomedicine Discovery Institute (BDI) and co-author of the study, emphasized: "The reason why viruses like rabies are deadly is that they can completely take over many life activities in infected cells: such as hijacking the protein manufacturing mechanism, interfering with the information transmission 'postal system' within the cell, and even shutting down the defense mechanism that is supposed to protect the body's safety."
"Scientists have always been puzzled: How can viruses achieve such complex control with so few genes? For example, rabies virus only has about five proteins, while human cells have more than 20,000."
Dr. Rawlinson of BDI's Mosley Laboratory, who is the co-first author of the paper, said that understanding how a very small number of viral proteins can perform so many tasks will help find new ways to intervene in infections. "Our research gives the answer. We found that P protein, a key protein of rabies virus, has multiple functions due to its ability to deform and bind to RNA."
"It is worth mentioning that RNA is the core component of the current new generation of RNA vaccines; within cells, RNA is responsible for important responsibilities such as transmission of genetic information, regulation of immune responses, and manufacturing of life building blocks."
Professor Gooley, head of the Gooley Laboratory at the University of Melbourne, is a co-author of the paper. He added: By locking the RNA system, the rabies virus P protein can switch different physical "states" within the cell, penetrate into multiple liquid cell compartments, take over important links, and turn the cell into a highly efficient virus factory.
"Although this study focuses on rabies viruses, similar strategies are likely to be used by high-risk viruses such as Nipah and Ebola. Understanding this new mechanism will bring great hope for the development of new antiviral drugs or vaccines that specifically block viral variability."
Dr. Rawlinson emphasized that this discovery will redefine the scientific community's understanding of "multifunctional viral proteins." "In the past, this type of protein was often compared to a train assembled from many 'carriages', with each 'carriage' (module) performing its own role. According to the traditional view, shortening the protein should lose the corresponding function. But the reality is that some shorter viral proteins have gained new functions. Our research shows that multifunctionality comes not only from the combination of modules, but also from the overall structural changes of these modules after they interact with each other - such as the formation of new RNA-binding abilities."
Associate Professor Mosley added that this ability to bind RNA allows viral proteins to shuttle freely among various liquid compartments within the cell. "In this way, it can enter and manipulate many cellular compartments that control key processes such as immune defense and protein synthesis. Our research provides a new explanation for the mechanism by which viruses use limited genes to make flexible, plastic and complex-controlling proteins."
The study was participated by a number of Australia's top scientific research institutions, including Monash University, the University of Melbourne, the Australian Nuclear Science and Technology Organization (Australian Synchrotron Radiation Light Source), the Doherty Institute of Infection and Immunity, the Australian Commonwealth Science and Industry Organization (CSIRO), the Australian Center for Disease Control and Prevention (ACDP) and Deakin University.
Compiled from /ScitechDaily