Multipartite viruses have one of the most puzzling genetic organizations found in living organisms. These viruses have several genome segments, each containing only a part of the genetic information, and each individually encapsidated into a separate virus particle. While countless studies on molecular and cellular mechanisms of the infection cycle of multipartite viruses are available, just as for other virus types, very seldom is their lifestyle questioned at the viral system level. Moreover, the rare available “system” studies are purely theoretical, and their predictions on the putative
benefit/cost balance of this peculiar genetic organization have not received experimental support. In light of ongoing progresses in general virology, we here challenge the current hypotheses explaining the evolutionary success of multipartite viruses and emphasize their shortcomings. We also discuss alternative ideas and research avenues to be explored in the future in order to solve the long-standing mystery of how viral systems composed of interdependent but physically separated information units can actually be functional.
The perusal of the literature presented above illustrates our current ignorance on the reasons explaining why multipartite viruses are so successful. The simple fact that they can be ssRNA, dsRNA, or ssDNA likely indicates that multi-encapsidation has evolved more than once, and yet we are unable to confirm any associated beneficial aspects. The proposed putative benefits are not yet convincing because of a lack of data, and because most also appear valid for segmented virus, thus not explaining multi-encapsidation. We believe further experimental work on the specifics of the biology of multipartite viruses is necessary to evaluate and challenge the existing hypotheses, and, even better, propose new ones perhaps more pertinent or unforeseen. A possibility that should not be ignored is that, because multipartitism most likely evolved independently several times, its evolution may have responded to distinct selection pressures: it is possible that the reasons that led to the evolution of multipartitism differ in different groups of viruses and that potential benefits that exist in one group do not exist in another. As concluding remarks, we outline a few research lines that could clarify or assign specific properties to multipartite viruses that we judge immediately critical.
Structural, physical, and biochemical properties of the virus particles depending on the contained segment(s) should be investigated in more detail. An important outreach of these studies (detailed in section 4) is that distinct properties of particles containing different segments may reflect an adaptive process involved in the temporal regulation of gene expression specific to multipartite viral systems. Although such variable particle properties were shown to be related to the RNA folding structure, they may also be important for multipartite ssDNA viruses in which secondary/tertiary folding structures of various segments appear to have unknown biological functions [97].
Also related to the regulation of gene expression, the discovery of the genome formula in populations of the nanovirus FBNSV [50] contributes to the consideration of a putative important role of gene copy number variations in the biology of viruses. Prominent questions are whether the genome formula is also controlled in other multipartite viruses, whether it actually regulates gene and phenotype expression, and whether it is an adaptive and evolvable trait. While arguments in favor of the adaptive regulation of gene copy number in multipartite viruses are discussed in section 3, a direct experimental demonstration is still lacking.
