Structural Virology

  HEADFélix REY /

  Annual Report

The “Unité de Virologie Structurale” (UVS) was formally created in October 2005, and the laboratory space was available in November 2006. The scientific goals of this research unit are twofold: 1- to provide a structural basis for understanding the molecular mechanism used by enveloped viruses to induce fusion of the viral and cellular membranes during entry, and 2- to study the structure of RNA-dependent RNA polymerases and associated replication enzymes, in order to understand the mechanism of genome replication of RNA viruses. In both points 1 and 2, the studies concern mostly viruses of global public health or of veterinary importance, and the knowledge gained can be used for translational structure-based design of preventive or curative antiviral agents. In addition, the structural studies often provide unexpected information about evolutionary relations between viruses of different categories.

Our previous work in the field of viral envelope proteins led to the identification of a new structural class of viral membrane fusion proteins, class II, which currently includes the envelope proteins of flaviviruses and alphaviruses only.

Like class I proteins (the prototype of which is the influenza virus hemagglutinin), class II proteins adopt a hairpin conformation to cause membrane fusion, but the architecture of the molecule – composed essentially of beta-sheets – is radically different from class I. Very recently, in collaboration with Yves Gaudin in Gif-sur-Yvette, we determined the 3D structure of the rhabdovirus G glycoprotein which displays properties from both structural classes, and is homologous to glycoprotein gB of herpes viruses, revealing a totally unexpected evolutionary link.

One of the main projects of the UVS is to extend the structural studies to viruses that are expected to have membrane fusion proteins of class II because of similarities in the arrangement of the structural-protein genes in the viral genome. The obvious initial targets are viruses belonging to the same family (the Flaviviridae family also includes the hepatitis C virus, the pestiviruses and the GB viruses and the Togaviridae family which includes alphaviruses and rubella virus. It is important to collect new information on the envelope proteins of these viruses in order to understand the extent of class II and the tolerated variations compatible with their function. At this point, we are concentrating our efforts in the production of recombinant viral glycoproteins for crystallization trials, and very recently – almost concomitantly with our installation in the renovated laboratory - we have obtained crystals of the pestivirus glycoprotein E2 (Figure).



Publications 2006 of the unit on Pasteur's references database

Activity Reports 2006 - Institut Pasteur
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