Genetic analysis of a poliovirus/hepatitis C virus (HCV) chimera: interaction between the poliovirus cloverleaf and a sequence in the HCV 5' nontranslated region results in a replication phenotype.
Internal ribosomal entry sites (IRESs) can function in foreign viral genomes or in artificial dicistronic mRNAs. We describe an interaction between the wild-type hepatitis C virus (HCV)-specific sequence and the poliovirus (PV) 5'-terminal cloverleaf in a PV/HCV chimeric virus (containing the HCV IRES), resulting in a replication phenotype. Either a point mutation at nucleotide (nt) 29 or a deletion up to nt 40 in the HCV 5' nontranslated region relieved the replication block, yielding PV/HCV variants replicating to high titers. Fortuitous yet crippling interactions between an IRES and surrounding heterologous RNA must be considered when IRES-based dicistronic expression vectors are being constructed.
Zhao
W D
WD
Department of Molecular Genetics and Microbiology, State University of New York at Stony Brook, 11794-5222, USA.
Lahser
F C
FC
Wimmer
E
E
D020121:5' Untranslated Regions; D006367:HeLa Cells; D016174:Hepacivirus / Q000235:genetics* / Q000502:physiology; D006801:Humans; D009690:Nucleic Acid Conformation; D010641:Phenotype; D017955:Poliovirus / Q000235:genetics*; D011995:Recombination, Genetic; D014779:Virus Replication
D020121:5' Untranslated Regions