Université François Rabelais, Inserm ERI19 et Service de biochimie et biologie moléculaire, CHRU, Tours
Among eukaryotic cell-expression-systems, the one derived from alphaviruses, including Semliki forest virus (SFV), offers an efficient method for protein production in mammalian cells. Despite this efficacy, twenty years after their discovery alphaviruses vectors remain poorly used. Alphavirus vectors exist as naked RNA vectors or as recombinant particles. The use of costly RNA-based replicons, and the fact that production of recombinant particles is a complex process to carry out, have hampered the attractiveness of the methods. Lastly, the apoptotic signals induced by alphavirus vectors replication leads to a rapid death of the producing cells. This feature, which can be detrimental in vitro, is advantageously exploited for in vivo applications. Besides laboratory applications, alphavirus vectors have been explored in rare phase I clinical trials, for vaccine development and cancer gene therapy, therefore, alphavirus vector will benefit from the advent of new, biosafety-efficient, methods for particles production. Most of the recent advances in the field proposed an heterologous mobilisation of alphavirus replicon. While increasing biosafety aspects, new methods are also simpler regarding the genesis of recombinant particles. In the present review, we overview the alphavirus life cycle with a special attention to the features influencing vector design and utility.