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Mystery Solved: How the Flu Virus Makes More of Itself (2006)

Like all viruses, the flu virus uses machinery inside a cell to make copies of itself. But the precise mechanism by which viral genes are assembled and packaged into a new virus particle (called a virion) has long been a matter of debate. Some scientists have argued that the eight segments of RNA that make up the flu virus genome are arranged randomly in each young virion. However, a chance observation by NIAID grantee Yoshihiro Kawaoka, D.V.M, Ph.D., and his colleagues at the University of Wisconsin-Madison School of Veterinary Medicine led to the discovery that the genes are instead arranged into the same pattern each time a new virion is formed.

Using a method of microscopy called electron tomography, the researchers captured three-dimensional images of flu viruses as they assembled into virions. The technique allowed the scientists to see cross-sectional “slices” of the virions. The team discovered that flu’s eight genes invariably arrange into a daisy-like pattern of seven rod-shaped structures spaced evenly around a central core.

Gene arrangement in flu virus replication. Illustration
Genes arranged systematically during flu virus replication. View larger image. Credit: NIAID

The finding was published in the journal Nature in 2006. It could influence approaches to developing new drugs and vaccines to fight flu. Knowing that genes are always arranged in the same way in each virion, notes Dr. Kawaoka, raises the possibility that drugs could be designed to interrupt the process of replication.

The first hint that flu genetic material is packaged systematically came after the serendipitous observation that electron micrographs of freeze-dried flu viruses sometimes caught a cell in the process of releasing new virions. In the micrographs, a distinct image of seven dots arrayed around a central speck could frequently be seen. The subsequent imaging by electron tomography proved those dots and specks were, in fact, the genetic material of the flu virus.


T Noda et al. Architecture of ribonucleoprotein complexes in influenza A virus particles. Nature 439(7075):490-2. DOI: 10.1038/nature04378 (2006).

Last Updated March 12, 2013

Last Reviewed March 12, 2013