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RESEARCH PRODUCT

The effect of genetic complementation on the fitness and diversity of viruses spreading as collective infectious units

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Viruses can spread collectively using different types of structures such as extracellular vesicles, virion aggregates, polyploid capsids, occlusion bodies, and even cells that accumulate virions at their surface, such as bacteria and dendritic cells. Despite the mounting evidence for collective spread, its implications for viral fitness and diversity remain poorly understood. It has been postulated that, by increasing the cellular multiplicity of infection, collective spread could enable mutually beneficial interactions among different viral genetic variants. One such interaction is genetic complementation, whereby deleterious mutations carried by different genomes are compensated. Here, we used simulations to evaluate whether complementation is likely to increase the fitness of viruses spreading collectively. We show that complementation among co-spreading viruses initially buffers the deleterious effects of mutations, but has no positive effect on mean population fitness over the long term, and even promotes error catastrophe at high mutation rates. Additionally, we found that collective spread increases the risk of invasion by social cheaters such as defective interfering particles. We also show that mutation accumulation depends on the type of collective infectious units considered. Co-spreading viral genomes produced in the same cell (e.g. extracellular vesicles, polyploid capsids, occlusion bodies) should exhibit higher genetic relatedness than groups formed extracellularly by viruses released from different cells (aggregates, binding to bacterial or dendritic cell surfaces), and we found that increased relatedness limits the adverse effects of complementation as well cheater invasion risk. Finally, we found that the costs of complementation can be offset by recombination. Based on our results, we suggest that alternative factors promoting collective spread should be considered.