Harvard Medical School,
Department of Microbiology and Molecular Genetics,
New Research Building, Rm. 940
77, avenue Louis-Pasteur, Boston, MA 02115, États-Unis
Mononegavirales comprises viruses representing a large variety of human, animal and plant pathogens. These viruses have a non-segmented negative stranded RNA genome encoding their own RNA dependent RNA polymerase, the large protein L used to transcribe and replicate their genome. Due to the absence of methods to produce purified recombinant L proteins, these later were poorly characterized. Recently, the vesicular stomatitis virus L protein has been purified and used for structural and functional analysis. Electron microscopy images of L provided the first structural insight into the molecular architecture of L, and its conserved regions were mapped. Moreover, a new
in vitro assay was developed and the mechanism by which L initiates RNA synthesis has been characterized, as well as the effects of its co-factor, the phosphoprotein P, on its own activity. This system constitutes a powerful tool to screen inhibitors directed specifically against the polymerase activity of L. These data have led to significant progress into the understanding of how the replicative machinery of these viruses function.