Scientists describe elusive replication machinery of flu viruses

Scientists at The Scripps Research Institute have made a major advance in understanding how flu viruses replicate within infected cells. The researchers used cutting-edge molecular biology and electron-microscopy techniques to ''see'' one of influenza's essential protein complexes in unprecedented detail. The images generated in the study show flu virus proteins in the act of self-replication, highlighting the virus's vulnerabilities that are sure to be of interest to drug developers.

The report, which appeared online in Science Express on 22 November 2012, focuses on influenza's ribonucleoprotein (RNP). RNPs contain the virus's genetic material plus the special enzyme that the virus needs to make copies of itself.

''Structural studies in this area had stalled because of the technical obstacles involved, and so this is a welcome advance,'' said Ian A Wilson, the Hansen Professor of Structural Biology at TSRI and senior author of the report with TSRI professors of cell biology Bridget Carragher and Clint Potter. ''The data from this study give us a much clearer picture of the flu virus replication machinery.''

Unveiling the Mystery of RNPs
At the core of any influenza virus lie eight RNPs, tiny molecular machines that are vital to the virus's ability to survive and spread in its hosts. Each RNP contains a segment - usually a single protein-coding gene - of the RNA-based viral genome. This viral RNA segment is coated with protective viral nucleoproteins and has a structure that resembles a twisted loop of chain.

The free ends of this twisted loop are held by a flu-virus polymerase enzyme, which handles the two central tasks of viral reproduction: making new viral genomic RNA, and making the RNA gene-transcripts that will become new viral proteins.

Aside from its importance in ordinary infections, the flu polymerase contains some of the key ''species barriers'' that keep, for example, avian flu viruses from infecting mammals.