The genome and its manipulation: Recovery of the 1918 virus and vaccine virus generation

Reverse genetics, which allows the generation of influenza viruses from cloned cDNAs, has enabled the recreation of the pandemic 1918 virus based on viral sequences extracted from preserved samples. Studies with wild-type and reassortant 1918 viruses have revealed the first clues to the unprecedented pathogenicity of this virus. In particular, the hemagglutinin (HA) and polymerase genes of the pandemic virus are now known to contribute to its exceptional virulence. Reverse genetics has also been used to generate vaccine viruses, including candidate vaccines to highly pathogenic avian influenza viruses. Thus, the ability to generate influenza viruses at will has considerably advanced basic influenza virology and the development of novel influenza vaccines.