Inspecting Influenza

Two independent teams of researchers have gotten the first look at the three-dimensional arrangement of the influenza virus’s genome and its associated proteins. The 20-Å structure sets the foundation for studying the virus’s life cycle and developing therapies to combat the human pathogen. The virus causes frequent epidemics, killed tens of millions in a 1918 pandemic, and could cause another round of devastation in the future.

The influenza virus genome is composed of eight single strands of RNA that fold back on themselves to form eight hairpinlike structures, says Juan Ortín at the Spanish National Centre for Biotechnology in Madrid, who led one of the structure-solving teams with his colleague Jaime Martín-Benito (Science, DOI: 10.1126/science.1228172). An independent team at Scripps Research Institute led by Ian A. Wilson and Bridget Carragher also reports a similar influenza structure (Science, DOI: 10.1126/science.1227270).

Along the length of each hairpin, the two arms of the single-stranded RNA twist into a helix that looks at first glance “surprisingly like DNA,” Ortín says. For example, the RNA hairpin’s helical twists have a major and minor groove similar to those of DNA.

But unlike DNA, the two strands in the RNA hairpin don’t acquire their helical structure from base-pairing, Ortín adds. Instead, specific viral proteins located regularly along the hairpin provide the scaffolding for the helical twists. The Spanish and American teams both found a polymerase protein complex sitting on top of each RNA hairpin.

“Three-dimensional reconstruction of the influenza virus ribonucleoprotein has long been considered challenging because of its small size, short length, high flexibility, and structural instability,” note Yizhi Jane Tao and Wenjie Zheng of Rice University in a commentary (Science, DOI: 10.1126/science.1231588). Both teams made use of 3-D electron microscopy to get similar reconstructions, the main differences being variations in some of the RNA’s helical parameters and orientations of the RNA-associated proteins, Tao and Zheng note.

The structures reported “will have a tremendous impact on our understanding of influenza virus transcription and replication, ribonucleoprotein intracellular transport, and virus assembly,” Tao and Zheng add. “Further studies of this kind would allow scientists to address many long-standing questions.”