Expanding use of multi-origin subcellular membranes by positive-strand RNA viruses during replication

Positive-strand RNA viruses utilize various subcellular membrane surfaces for replication. The subverted membranes facilitate the assembly of viral replication complexes by sequestering viral and co-opted host proteins to reach high local concentrations and protect viral RNAs from destruction by host antiviral responses. In this review, we discuss that tombusviruses and nodaviruses are capable of exploiting alternative subcellular membranes in cells and in vitro in the absence of primary membranes targeted by these viruses or when the replication proteins are retargeted. The roles of protein factors and lipids and membrane contact sites in replication site selection are also discussed. Surprisingly, tombusviruses could also exploit expanded ER membranes, which provide enhanced subcellular environment for replication. The expanded ER membranes are formed due to deletion of a lipin homolog, which is responsible for de novo lipid synthesis and formation of lipid droplets, suggesting that host genes connected to genetic diseases affect virus replication. Overall, these viruses show remarkable flexibility in utilizing various subcellular membranes for replication under different conditions.