Transcription et réplication des Mononegavirales : une machine moléculaire originale

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.