Structure of Rabies Virus Nucleocapsid Revealed

Researchers have found how RNA viruses such as rabies, measles, and Ebola protect the genetic information contained in their single strand of RNA from destruction by the human innate immune system.

Investigators at the Institut de Virologie Moléculaire et Structurale (IVMS, Grenoble, France) and the European Molecular Biology Laboratory (Grenoble, France) bombarded crystals of rabies virus RNA bound to nucleoprotein--a structure called a nucleocapsid--with high-intensity x-rays. A scattering pattern with resolution of 3.5 angstroms was obtained showing an undecameric (11-member) ring.

The structural evidence allowed the investigators to propose in the June 15, 2006, online edition of Science that polymerization of the nucleoprotein was achieved by domain exchange between protomers, with flexible hinges allowing nucleocapsid formation. The two core domains of the nucleoprotein were clamped around the RNA at their interface and shielded it from the environment.

"Nucleoprotein is vital for the rabies virus,” explained senior author Dr. Rob Ruigrok, director of the IVMS. "It is one of the few proteins that the virus brings into the host cell and it wraps around the RNA like a protection shield. Without this shield the RNA would be degraded by the enzymes of the human immune system that try to eliminate the invader. This dynamic mechanism makes nucleoproteins an excellent drug target. Small agents that bind to the protein in such a way to block its flexibility and keep it in the closed state would prevent replication of the virus and would stop it from spreading.”



Related Links:
Institut de Virologie Moléculaire et Structurale
European Molecular Biology Laboratory