Investigating the Mechanisms of Paramyxovirus Assembly: Implications for Antiviral Therapeutic Design

Paramyxoviruses are a group of highly infectious and potentially lethal human and animal pathogens with pandemic potential. Notable examples of paramyxoviruses include measles and parainfluenza viruses, which affect millions of people each year, and Nipah virus, which is rare, but almost always fatal. Unfortunately, there are currently no treatments available for any paramyxovirus. As viral assembly pathways provide a good target for drug development, our work will focus on characterizing paramyxovirus viral assembly in an effort to identify weak points that could be used for the development of new therapeutics. Paramyxovirus particles are made up of only six structural proteins, among which the matrix protein is of particular importance due to its central role in the assembly and release of new virus particles. When a cell is infected, paramyxoviruses produce many copies of the matrix protein, which then attach to the inner surface of the infected cell membrane to form an interlocking network. This network of matrix proteins helps to assemble new virus particles, which are released from the host cell and go on to infect other individuals. Despite ongoing research efforts, the process of how matrix proteins assemble and how they interact with other components of the virus and the host cell remains poorly understood. Thus, the goal of this research is to understand the underlying structures and processes involved in the formation and release of paramyxovirus particles. We will use a combination of advanced imaging techniques and laboratory experiments to figure out the process of how matrix proteins join together to form the interlocking network and what role membrane lipids play in putting together the virus particles. This research will give us a better understanding of the viral life cycle and will provide a roadmap for the design of new, effective antiviral drugs to protect against these deadly viruses.