Abstract
Nonretroviral integrated RNA viruses (NIRVs) are genes of nonretroviral RNA viruses found in the genomes of many eukaryotic organisms. NIRVs are thought to sometimes confer virus resistance, meaning that they could impact spread of the virus in the host population. However, a NIRV that is expressed may also impact the evolution of virus populations within host organisms. Here, we experimentally addressed the evolution of a virus in a host expressing a NIRV using Tobacco etch virus (TEV), a plant RNA virus, and transgenic tobacco plants expressing its replicase, NIb. We found that a virus missing the NIb gene, TEV-ΔNIb, which is incapable of autonomous replication in wild-type plants, had a higher fitness than the full-length TEV in the transgenic plants. Moreover, when the full-length TEV was evolved by serial passages in transgenic plants, we observed genomic deletions within NIb--and in some cases the adjacent cistrons--starting from the first passage. When we passaged TEV and TEV-ΔNIb in transgenic plants, we found mutations in proteolytic sites, but these only occurred in TEV-ΔNIb lineages, suggesting the adaptation of polyprotein processing to altered NIb expression. These results raise the possibility that NIRV expression can indeed induce the deletion of the corresponding genes in the viral genome, resulting in the formation of viruses that are replication defective in hosts that do not express the same NIRV. Moreover, virus genome evolution was contingent upon the deletion of the viral replicase, suggesting NIRV expression could also alter patterns of virus evolution.