Reverse genetics of influenza virus

Reverse genetics of negative-sense RNA viruses, which enables one to genera te virus entirely from cloned cDNA, has progressed rapidly over the past de cade. However, despite the relative ease with which nonsegmented negative-s ense RNA viruses can now be produced from plasmids, the ability to generate viruses with segmented genomes has lagged considerably, largely because of the inherent technical difficulties in providing all viral RNAs and protei ns from cloned cDNA. A breakthrough in reverse genetics technology in the i nfluenza virus field came in 1999, when we (Neumann et. al., 1999, Proc. Na tl. Acad. Sol. USA 96, 9345-9350) and others (Fodor et al, 1999, J. Virol. 73, 9679-9682) exploited a new approach to viral RNA production. In this re view, we discuss the background for this advance, the systems that are now available for the generation of influenza viruses, and the implications of these developments for the future of virus research. (C) 2001 Academic Pres s.