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Rewiring the RNAs of Influenza Virus to Prevent Reassortment
Qinshan Gao and Peter Palese
Proceedings of the National Academy of Sciences of the United States of America
Vol. 106, No. 37 (Sep. 15, 2009), pp. 15891-15896
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/40484818
Page Count: 6
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Influenza viruses contain segmented, negative-strand RNA genomes. Genome segmentation facilitates reassortment between different influenza virus strains infecting the same cell. This phenomenon results in the rapid exchange of RNA segments. In this study, we have developed a method to prevent the free reassortment of influenza A virus RNAs by rewiring their packaging signals. Specific packaging signals for individual influenza virus RNA segments are located in the 5' and 3' noncoding regions as well as in the terminal regions of the ORF of an RNA segment. By putting the nonstructural protein (NS)-specific packaging sequences onto the ORF of the hemagglutinin (HA) gene and mutating the packaging regions in the ORF of the HA, we created a chimeric HA segment with the packaging identity of an NS gene. By the same strategy, we made an NS gene with the packaging identity of an HA segment. This rewired virus had the packaging signals for all eight influenza virus RNAs, but it lost the ability to independently reassort its HA or NS gene. A similar approach can be applied to the other influenza A virus segments to diminish their ability to form reassortant viruses.
Proceedings of the National Academy of Sciences of the United States of America © 2009 National Academy of Sciences