Engineering influenza viral vectors

Abstract

The influenza virus is a respiratory pathogen with a negative-sense, segmented RNA genome. Construction of recombinant influenza viruses in the laboratory was reported starting in the 1980s. Within a short period of time, pioneer researchers had devised methods that made it possible to construct influenza viral vectors from cDNA plasmid systems. Herein, we discuss the evolution of influenza virus reverse genetics, from helper virus-dependent systems, to helper virus-independent 17-plasmid systems, and all the way to 3- and 1- plasmid systems. Successes in the modification of different gene segments for various applications, including vaccine and gene therapies are highlighted.

Keywords: gene delivery; gene therapy; influenza virus; microRNA delivery; pseudo-typed virus; reverse genetics; vaccine; viral vector.

Figure 1. Technique evolution of influenza virus reverse genetics. Helper virus depended influenza reverse genetics system; (2) 17-plasmid influenza reverse genetics system. Eight plasmid for synthesis of RNA segments, and 9 plasmids for expression of structural proteins; (3) 8-plasmid influenza reverse genetics system. Each plasmid has PolII and PolI promoter sequence flanked by influenza gene segments; (4) 3-plasmid influenza reverse genetics system. One plasmid carries eight PolI promoter-driven vRNA transcription units. The second plasmid encodes polymerases, and the third one expresses NP; (5) one-plasmid influenza reverse genetics system.