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

Journal of Virology
Markus WolschekMichael Bergmann

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.

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Citations

Mar 2, 2013·Cell Death and Differentiation·R WeissM Bergmann
May 16, 2014·MBio·Julia DuboisManuel Rosa-Calatrava
Jun 21, 2012·Influenza and Other Respiratory Viruses·Othmar G Engelhardt
Nov 14, 2013·The Journal of General Virology·Irina KuznetsovaMichael Bergmann
Aug 28, 2012·Bioengineered·Junwei LiMingtao Zeng
Jul 16, 2016·The Journal of General Virology·Matteo Samuele PizzutoWendy S Barclay
Jun 29, 2021·Journal of Virological Methods·Peng YangShengqi Wang

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