• Open Access

Many ways to make an influenza virus – review of influenza virus reverse genetics methods


Othmar G. Engelhardt, Division of Virology, National Institute for Biological Standards and Control, Health Protection Agency, Blanche Lane, South Mimms, Potters Bar, EN6 3QG, UK. E-mail: othmar.engelhardt@nibsc.hpa.org.uk


Methods to introduce targeted mutations into a genome or, in the context of virology, into a virus are subsumed under the term reverse genetics (RG). Influenza viruses are important human pathogens that continue to surprise us. The development of RG for influenza viruses has greatly expanded our knowledge about influenza virus and enabled researchers to generate influenza viruses with rationally designed genotypes. Currently, a wide array of influenza virus RG methods is available. These can all be traced to fundamental principles essential in any RG system for negative-strand RNA viruses. This review gives an overview of these principles and of the multitude of RG methods, categorising them by technical characteristics.