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Press release | Virus | Immune system | DNA | Health ＆ life sciences
For the first time, the assembly of a key complex
of the measles virus, called nucleocapsid, has just been described in vitro.
The mechanisms of this assembly could pave the way for further anti-viral
development. Details are provided by researchers from the Institut de biologie structurale
(CEA/CNRS/Université Grenoble Alpes) in an article published on 6 June 2016 in Angewandte
When a host cell is infected, the Paramyxoviridae family (to which the measles virus belongs) protect their RNA genomes in nucleocapsids, very long helical structures made up of thousands of nucleo-proteins. The nucleocapsid formation process is essential for viral replication, and, as such, it presents a potentially promising drug target to treat these infections.
Until now, it has not been possible to shed light on the assembly process of these nucleocapsids ("encapsidation”), since the process could not be monitored in vitro. In this study, for the first time, researchers from IBS in Grenoble describe how this assembly occurs, using a combination of several techniques, such as nuclear magnetic resonance, fluorescence spectroscopy and electron microscopy.
By combining all these technologies, it was possible to monitor nucleocapsid assembly: adding RNA molecules to a protein isolate solution, which self-assembled on the RNA scaffolding. The researchers were then able to observe the assembly process in real-time, i.e. the in vitro duplication of what happens in an infected cell immediately after replication of the viral genome. The researchers then discovered that nucleocapsid assembly depends on the exact RNA sequence, a very surprising observation given that it is always necessary for the virus to fully protect its genome, whatever sequence is considered.This new research tool not only makes it possible to study the basis of molecular interaction between nucleo-proteins and RNA, but it also paves the way for several new applications. The potential for monitoring the effectiveness of genome encapsidation in different conditions could develop viral replication inhibitors, and gives hope for multiple applications in the nano-biotechnology sector or in the development of vaccinations.
Sigrid Milles, Malene Ringkjøbing Jensen, Guillaume Communie, Damien Maurin, Guy Schoehn, Rob W.H. Ruigrok and Martin Blackledge, Self-assembly of measles virus nucleocapsid-like particles: Kinetics and RNA sequence dependence, Angewandte Chemie, 6 June 2016. DOI: 10.1002/anie.201602619
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.