Journal
VIROLOGY
Volume 412, Issue 1, Pages 220-232Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2011.01.008
Keywords
Cyclization sequence; RNA-RNA interaction; West Nile virus; Replication efficiency; Plaque phenotype; Intracellular viral RNA; Mutagenesis; WNV infectious clone
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Funding
- National Institute of Allergy and Infectious Diseases, National Institutes of Health [AI048088]
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Mosquito-borne flavivirus genomes contain conserved 5' and 3' cyclization sequences (CYC) that facilitate long distance RNA-RNA interactions. In previous studies, flavivirus replicon RNA replication was completely inhibited by single or multiple mismatching CYC nt substitutions. In the present study, full-length WNV genomes with one, two or three mismatching CYC substitutions showed reduced replication efficiencies but were viable and generated revertants with increased replication efficiency. Several different three adjacent mismatching CYC substitution mutant RNAs were rescued by a second site mutation that created an additional basepair (nts 147-10913) on the internal genomic side of the 5'-3' CYC. The finding that full-length genomes with up to three mismatching CYC mutations are viable and can be rescued by a single nt spontaneous mutation indicates that more than three adjacent CYC basepair substitutions would be required to increase the safety of vaccine genomes by creating mismatches in inter-genomic recombinants. (c) 2011 Elsevier Inc. All rights reserved.
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