Open AccessThe flavivirus polymerase NS5 regulates translation of viral genomic RNA
Author(s) -
Teodoro Fajardo,
Thomas J Sanford,
Harriet V Mears,
Annika Jasper,
Skye Storrie,
Daniel Santos Mansur,
Trevor R. Sweeney
Publication year - 2020
Publication title -
nucleic acids research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.008
H-Index - 537
eISSN - 1362-4954
pISSN - 0305-1048
DOI - 10.1093/nar/gkaa242
Subject(s) - biology , translation (biology) , flavivirus , polymerase , internal ribosome entry site , viral replication , rna , virology , rna dependent rna polymerase , rna polymerase , genetics , genome , ribosome , virus , gene , messenger rna
Flaviviruses, including dengue virus and Zika virus, contain a single-stranded positive sense RNA genome that encodes viral proteins essential for replication and also serves as the template for new genome synthesis. As these processes move in opposite directions along the genome, translation must be inhibited at a defined point following infection to clear the template of ribosomes to allow efficient replication. Here, we demonstrate in vitro and in cell-based assays that the viral RNA polymerase, NS5, inhibits translation of the viral genome. By reconstituting translation in vitro using highly purified components, we show that this translation block occurs at the initiation stage and that translation inhibition depends on NS5-RNA interaction, primarily through association with the 5' replication promoter region. This work supports a model whereby expression of a viral protein signals successful translation of the infecting genome, prompting a switch to a ribosome depleted replication-competent form.