New Look at Influenza Virus

New pictures of the influenza virus have prompted scientists to rethink previous ideas of how the virus escapes from cells, according to a study by researchers from Japan, Sweden and the U.S. published in the Jan. 26 issue of Nature. The flu virus carries its genes in eight segments of RNA and proteins. Before escaping from a host cell, the virus has to assemble the right pieces and package them into a complete virus. Scientists think that shuffling these segments allows flu viruses to vary from year to year, producing new infectious strains. One theory held that the eight genetic segments are randomly packaged into viral particle, but only those with the right eight segments are viable. That would be inefficient, but would put a natural brake on growth rate of the virus. The new images, taken using a technique called cryoelectron microscopy, clearly show that the eight genetic segments are organized into a precise pattern, with seven segments surrounding a central one, before the virus particle wraps itself in an outer coating and membrane and buds out of the cell. "It was thought that viral RNA packaging often fails, but this is not true," said R. Holland Cheng, professor of molecular and cellular biology at UC Davis and one of the authors of the paper. In conventional electron microscopy, samples are "fixed" with heavy metals that deflect electrons, providing the image contrast. But that means that only the surface can be imaged, said Cheng. In cryoelectron microscopy, samples are fixed by rapid freezing to extremely low temperatures with liquid nitrogen or helium. Researchers then take pictures from different angles and reconstruct them with a computer to create a three-dimensional image. Cryoelectron microscopy can capture information that you cannot get with conventional electron microscopy, Cheng said. Cheng's laboratory is now using the technique to look deeper into the cell to find the "glue" that bundles together the genome segments of the virus. Before joining UC Davis in 2004, Cheng worked at the Karolinska Institute in Sweden. The other authors on the study are Takeshi Noda, Hiroshi Sagara, Ayato Takada and Yoshihiro Kawaoka of the University of Tokyo, Japan; Hiroshi Kida at Hokkaido University, Japan; and Albert Yen at the Karolinska Institute. The work was funded by the Japan Science and Technology Agency; the U.S. National Institutes of Health; and the Swedish Research Council.