John Libbey Eurotext

Virologie

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Transcription et réplication des Mononegavirales : une machine moléculaire originale Volume 16, issue 4, Juillet-Août 2012

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Authors
Aix-Marseille Université, CNRS, AFMB UMR 7257, 163, avenue de Luminy, Case 932, 13288 Marseille, France, Unit of Virus Host Cell Interactions, UMI 3265 UJF-EMBL-CNRS, 6, rue Jules-Horowitz, 38042 Grenoble cedex 9, France, Inra, unité de virologie et immunologie moléculaires (UR892), Jouy-en-Josas, France, Université Lyon-I, virologie humaine, Inserm U758, ENS Lyon, 21, avenue Tony-Garnier, 69007 Lyon, France

Viruses with a non-segmented negative-sense RNA genome, or Mononegavirales, are important pathogens for plants, animals and humans with major socio-economic and health impacts. Among them are well-known human pathogens such as measles, mumps and respiratory syncytial virus. Moreover, animal reservoirs appear much larger than previously thought, hence broadening the risk of emergence of life-threatening zoonotic viruses such as Rabies, Ebola, Marburg, Nipah or Hendra related viruses. These viruses have peculiar transcription and replication machinery that make them unique in the living world. Indeed, their genomic RNA, when naked, is non-infectious because it can be neither transcribed nor translated, and the L RNA-dependent RNA-polymerase is at best able to initiate the synthesis of an RNA copy of a few of tens of nucleotides in length. To serve as a template, the genomic RNA must be encapsidated in a helicoidal homopolymer made of a regular and continuous array of docked N protomers in which the ribose-phosphate backbone is fully embedded. This complex, or nucleocapsid, is recognized by the L polymerase thanks to its cofactor, the P protein, to sequentially transcribe the five genes into five processed mRNAs for the simplest viruses. Subsequently, a switch occurs and the polymerase replicates a full copy of antigenomic RNA that is concurrently encapsidated. This new template is then used for the production of new infectious genomic nucleocapsids. This review summarizes current structural, dynamic and functional data of this peculiar molecular machinery and provides a unified model of how it can function. It illuminates the overall common strategies and the subtle variations in the different viruses, along with the key role of the dual ordered/disordered structure of the protein components in the dynamics of the viral polymerase machinery.