New research reveals a previously unknown gene in influenza A viruses, which most frequently infect birds but have also caused pandemics in humans and other mammals. Although scientists have studied these viruses intensively, they still have a relatively poor understanding of the molecular interactions between the virus and its host. The new findings should help expand that picture and might suggest a useful target for antiviral therapies. Brett Jagger and colleagues have now discovered a new gene hidden away in this virus’ relatively small genome. Its protein is produced when the ribosome skips ahead while reading messenger RNA’s nucleotide chains. The ribosome reads the nucleotides in groups of three, so if it skips forward one nucleotide, it will read the nucleotides in different combinations. Jagger and colleagues report that such a “ribosomal frameshift” within the PA polymerase gene produces a protein they call PA-X. This protein inhibits the expression of RNA polymerase II, which is responsible for translating DNA into messenger RNA. In mice infected with a reconstructed version of the 1918 Spanish flu virus, PA-X influenced the expression of host genes required for cellular immune responses, implying that the protein affects the course of pathogenicity in animals.
Article #30: "In Influenza A Virus Segment 3 Modulates the Host Response," by B.W. Jagger; H.M. Wise; G.L. Bell; R.M. Dalton; A. Lo; S. Efstathiou; A.E. Firth; P. Digard at University of Cambridge in Cambridge, UK; B.W. Jagger; J.C. Kash; Y.-L. Xiao; R.L. Dunfee; L.M. Schwartzman; J.K. Taubenberger at National Institute of Allergy and Infectious Diseases, National Institutes of Health in Bethesda, MD; K.-A. Walters; A. Ozinsky at Institute for Systems Biology in Seattle, WA; N.M. Wills; J.F. Atkins at University of Utah in Salt Lake City, UT; J.F. Atkins at University College Cork in Cork, Ireland; H.M. Wise at University of Edinburgh in Scotland, UK; G.L. Bell at Cambridge Institute for Medical Research in Cambridge, UK; P. Digard at CSIC in Madrid, Spain.