title: A host Ca2+/Mn2+ ion pump is a factor in the emergence of viral RNA recombinants.
abstract: 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 approximately 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.
authors.affiliation: Department of Plant Pathology, University of Kentucky, Plant Science Building, Lexington, KY 40546, USA.
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Jaag
authors.forename: Judit
authors.initials: J
authors.lastname: Pogany
authors.forename: Peter D
authors.initials: PD
authors.lastname: Nagy
mesh_terms: D000252:Calcium-Transporting ATPases / Q000235:genetics / Q000502:physiology*; D003593:Cytoplasm / Q000737:chemistry; D055786:Gene Knockout Techniques; D008345:Manganese / Q000378:metabolism; D008954:Models, Biological; D018832:Molecular Chaperones / Q000235:genetics / Q000502:physiology*; D010935:Plant Diseases / Q000821:virology*; D012367:RNA, Viral / Q000235:genetics*; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000502:physiology* / Q000821:virology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*; D014026:Nicotiana / Q000821:virology; D017864:Tombusvirus / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication
chemical_list: D018832:Molecular Chaperones; D012367:RNA, Viral; C101767:SSC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D008345:Manganese; D000252:Calcium-Transporting ATPases