期刊
VIROLOGY
卷 421, 期 2, 页码 96-104出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2011.09.007
关键词
Flavivirus; Single-cycle virus; Chimera; RepliVAX; Packaging
类别
资金
- NIAID through the Western Regional Center of Excellence for Biodefense and Emerging Infectious Disease Research (NIH) [U54 AI057156]
- NIH [R21 AI077077, UO1 AI082960]
- Sealy Center for Vaccine Development (SCVD)
We previously described a single-cycle dengue vaccine (RepliVAX D2) engineered from a capsid (C) gene-deleted West Nile virus (WNV) expressing dengue virus serotype 2 (DENV2) prM/E genes in place of the corresponding WNV genes. That work demonstrated that adaptation of RepliVAX D2 to grow in WNV C-expressing cells resulted in acquisition of non-synonymous mutations in the DENV2 prM/E and WNV NS2A/NS3 genes. Here we demonstrate that the prM/E mutations increase the specific infectivity of chimeric virions and the NS2A/NS3 mutations independently enhance packaging. Studies with the NS2A mutant demonstrated that it was unable to produce a larger form of NS1 (NS1'), suggesting that the mutation had been selected to eliminate a ribosomal frame-shift slippage site in NS2A. Evaluation of a synonymous mutation at this slippage site confirmed that genomes that failed to make NS1' were packaged more efficiently than WT genomes supporting a role for NS1/NS1' in orchestrating virion assembly. (C) 2011 Elsevier Inc. All rights reserved.
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