Establishment of a chimeric, replication-deficient influenza A virus vector by modulation of splicing efficiency

J Virol. 2011 Mar;85(5):2469-73. doi: 10.1128/JVI.01650-10. Epub 2010 Dec 22.

Abstract

Segment 8 of the influenza A virus codes for two proteins (NS1 and NS2/NEP) via splicing. Here, we developed a viral vector expressing a cytokine or chemokine instead of the interferon antagonist NS1. To achieve both the desired genetic stability and high transgene expression levels, NS2/NEP mRNA splicing efficacy had to be fine-tuned by modification of splicing elements. Expression levels of secreted foreign proteins could be further enhanced by fusing the N-terminal 13 amino acids of NS1 with an IgK-derived secretion signal peptide. Thus, the first start codon was used for translation initiation of both NS2/NEP and the foreign protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Defective Viruses / genetics*
  • Defective Viruses / physiology
  • Gene Expression*
  • Genetic Vectors / genetics*
  • Genetic Vectors / physiology
  • Influenza A virus / genetics*
  • Influenza A virus / physiology
  • RNA Splicing*
  • Virus Replication