A Host Ca²⁺/Mn²⁺ Ion Pump Is a Factor in the Emergence of Viral RNA Recombinants

Viruses change rapidly due to genetic mutations, and viral RNA recombination in RNA viruses can lead to the emergence of drug-resistant or highly virulent strains. Here, we report that host Pmr1p, an ion pump that controls Ca²⁺/Mn²⁺ influx into the Golgi from the cytosol, affects the frequency of viral RNA recombination and the efficiency of replication. Inactivation of PMR1 leads to an ∼160-fold increase in RNA recombination of Tomato bushy stunt virus (TBSV) in yeast, a model host. Expression of separation-of-function mutants of Pmr1p reveals that the ability of Pmr1p to control the Mn²⁺ concentration in the cytosol is a key factor in viral RNA recombination. Indeed, a high Mn²⁺ concentration in a cell-free TBSV replication system increases the recombination frequency, and knockdown of Ca²⁺/Mn²⁺ exporters in plants increases virus replication and RNA recombination. Thus, a conserved host protein could affect the adaptive evolution of RNA viruses.