On the stability of sequences inserted into viral genomes

Willemsen, Anouk; Zwart, Mark P

The dsRNA viruses have a range of genome sizes (3.7-30.5 kb) that is similar to the ssDNA viruses. Most of the dsRNA viruses contain segmented genomes, where during replication, positivesense ssRNAs are packaged into procapsids and serve as templates for dsRNA synthesis. Thus, the progeny particles contain a complete set of equimolar genome segments. Proper recognition and stoichiometrical packaging of the ssRNAs is indispensable for multi-segmented genome assembly. Although, different dsRNA viruses employ different mechanisms for this assembly, these all rely on proper recognition of the ssRNAs in either specific RNA-protein or RNA-RNA interactions (Borodavka, Desselberger, and Patton 2018) . We therefore expect that dsRNA virus genomes are highly streamlined, since most gene insertions will probably disturb the recognition and packaging process of the ssRNAs. Interestingly, for rotaviruses it has been observed that genome segments containing sequence duplications are preferentially packaged into progeny viruses relative to wild-type segments (Troupin et al. 2011) , indicating that an increase in genome/segment size may not be a hard constraint. We hypothesize that few if any gene insertions will lead to viable genomes due to the perturbation of segmented genome assembly into virus particles. If a gene insertion happens to be viable, it will probably be rapidly purged from the viral genome. One exception to this hypothesis could be a gene insertion originating from a closely related virus, for example a virus with similar packaging signals, leading to a fitness advantage, such as increased packaging efficiency.