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Baylor College of Medicine News

Scientists capture structure of virus changing during infection

The mechanism of interaction between Prochloroccus, the most abundant photosynthetic microbe in the ocean, and a cyanophage that infects it has recently been unveiled.

Using intricate scientific techniques that involved freezing bacteria and virus and transporting them from Massachusetts to Houston in liquid nitrogen, scientists at Baylor College of Medicine and the Massachusetts Institute of Technology in Cambridge, Mass., used powerful cryo-electron microscopes to determine how the structure of the virus changes during infection, allowing it to release its DNA into the cell.

Seeing virus infect cell

"We are actually looking at the virus while it infects the cell," said Dr. Wah Chiu, professor of biochemistry and molecular biology at BCM and director of the National Center for Macromolecular Imaging at BCM. He is a senior author of the report that appears online today in the journal Nature Structural and Molecular Biology.

He and his colleagues used techniques called cryo-electron microscopy and cryo-electron tomography to view the bacteria and virus and powerful computers and software to assemble three-dimensional images of the organisms.

"Biophysicist Xiangan Liu developed a novel algorithm to discover the complex architectural details of the purified viruses with and without the genome," said Chiu.

Six-tailed phage (virus)

The virus or phage called P-SSP7 has six tails that act almost like the fins of a rocket as it lands on the foreign surface of the bacterial cell.

"Our paper suggests that when the virus lands on the surface, the six tails undergo a structural change," said Chiu. That enables them open a "valve" in the nozzle connecting to the six tails. The virus' DNA leaves through this nozzle and enters the cell's cytoplasm – infecting the cell.

Mechanical process

"We think this is a mechanical process," said Chiu. "The six tails of the virus land in the right spot and induce a conformation change. The virus has multiple proteins to facilitate the DNA release to the infecting cell. The tails are one protein. Another protein makes contact with the cell's membrane. That protein has a gate or a door. The configuration of the tail literally opens a door in the virus, triggering release of the DNA."

His main MIT collaborator, Dr. Sallie W. Chisholm, is one of the world's experts on Prochloroccus. Phage experts from her research group, Matthew Sullivan and Marcia Osburne, contributed essential knowledge of the cells' growth cycle and its interaction with the phage toward the success of the experiment, said Chiu.

Cryo-electron microscopy begins with freezing the sample to be viewed under the microscope so quickly that it cannot form crystals. It is then exposed to a stream of high energy particles known as an electron beam. The interaction of beam and sample form the resulting high resolution image. The novel software developed by Xiangan Liu and Matthew Baker has allowed them to describe the phage and bacterium in three-dimensional movies.

Others who took part in this work include Xiangan Liu, Qinfen Zhang, Kazuyoshi Murata, Matthew L Baker, Caroline Fu, Matthew T Dougherty and Michael F Schmid, of BCM. Zhang is also of Sun Yat-Sen University in Guangzhou, China. Sullivan is now of the University of Arizona in Tucson.

Funding for this work came from the U.S. National Institutes of Health, the U.S. National Science Foundation, the Robert Welch Foundation, the U.S. Department of Energy and the Gordon and Betty Moore Foundation.