Romain Gallet, Jérémy Di Mattia, Sébastien Ravel, Jean-Louis Zeddam, Renaud Vitalis, Yannis Michalakis, Stéphane Blanc, Plant Health Institute of Montpellier (UMR PHIM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Montpellier (UM), Centre de Biologie pour la Gestion des Populations (UMR CBGP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, Département Systèmes Biologiques (Cirad-BIOS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), This work was funded by French national institutions INRAE, CNRS, IRD, the French National Research Agency (ANR), and Montpellier University of Excellence (MUSE). This work was supported by the ANR grants `Nano' (ANR-14-CE02-0014) and `Nanovirus' (ANR-18-CE92-0028-01) and by MUSE (project BLANC-MUSE2020Multivir)., ANR-14-CE02-0014,Nano,Exploration de la biologie des virus multipartite(2014), ANR-18-CE92-0028,Nanovirus,Aspects moléculaires et cellulaires du cycle de vie des virus multipartites: les nanovirus(2018), and ANR-16-IDEX-0006,MUSE,MUSE(2016)
Multipartite viruses have a segmented genome, with each segment encapsidated separately. In all multipartite virus species for which the question has been addressed, the distinct segments reproducibly accumulate at a specific and host-dependent relative frequency, defined as the ‘genome formula’. Here, we test the hypothesis that the multipartite genome organization facilitates the regulation of gene expression via changes of the genome formula and thus via gene copy number variations. In a first experiment, the faba bean necrotic stunt virus (FBNSV), whose genome is composed of eight DNA segments each encoding a single gene, was inoculated into faba bean or alfalfa host plants, and the relative concentrations of the DNA segments and their corresponding messenger RNAs (mRNAs) were monitored. In each of the two host species, our analysis consistently showed that the genome formula variations modulate gene expression, the concentration of each genome segment linearly and positively correlating to that of its cognate mRNA but not of the others. In a second experiment, twenty parallel FBNSV lines were transferred from faba bean to alfalfa plants. Upon host switching, the transcription rate of some genome segments changes, but the genome formula is modified in a way that compensates for these changes and maintains a similar ratio between the various viral mRNAs. Interestingly, a deep-sequencing analysis of these twenty FBNSV lineages demonstrated that the host-related genome formula shift operates independently of DNA-segment sequence mutation. Together, our results indicate that nanoviruses are plastic genetic systems, able to transiently adjust gene expression at the population level in changing environments, by modulating the copy number but not the sequence of each of their genes.