An Early Step in Dengue Infection Visualized

Using cryo-electron microscopy, investigators at Purdue University have visualized one of the first steps in the dengue infection: an attachment of the virus to a protein on a cell’s surface:

During the earliest stages of infection, the dengue virus attaches to the “carbohydrate recognition domain,” or CRD, of a key binding protein called DC-SIGN, located on a host cell’s surface…
“We and others think that this CRD acts sort of like Velcro to get the virus to stick to the surface of the cell, although this has not been proven,” Kuhn said [Richard J. Kuhn, a professor and chair of Purdue’s Department of Biological Sciences -ed]. “Once the virus and protein receptor are linked, perhaps the virus then moves across the cell surface to find a second protein, attaching to that receptor and entering the cell.
“One of the things that this study shows is that only a very small portion of the cell’s surface is occupied by the DC-SIGN molecule, which means a significant amount of space is still available for that other receptor protein that people don’t know about yet.”
Zhang [Ying Zhang, a post-doctoral research associate -ed.] said that the initial binding of the CRD and the virus might result in a “signaling event between the DC-SIGN molecule and the other primary receptor, leading to activating the other protein and promoting the cell for infection.”
The virus has a diameter of 50 nanometers, or billionths of a meter, and the CRD is 3 nanometers wide.
In cryo-electron microscopy, specimens are first frozen before they are studied with an electron microscope. The method enables scientists to study details as small as 8 angstroms, or .8 nanometers, resolution high enough to see groups of atoms. An angstrom is one ten-billionth of a meter, or roughly a millionth as wide as a human hair.
Zhang discovered that the CRD attaches to a structure on the virus surface that contains two carbohydrates a distance of 18 angstroms apart. This feature apparently is essential for the binding to take place, she said.
“Why doesn’t the binding happen at other sugar-binding sites?” she asked. “The answer is that we need two carbohydrate sites that are 18 angstroms apart. There are no other sites that are 18 angstroms apart.”

Image caption: In the picture, the DC-SIGN molecule is represented as a string-like green structure connected to the CRD, which is binding to a virus particle, pictured as a spherical green object. Using a powerful imaging tool called cryo-electron microscopy, biologists at Purdue University took electron microscope pictures of the virus attached to the CRD shortly after the two joined together. It is the first time scientists have visualized the virus and CRD binding. (Graphic/Department of Biological Sciences, Purdue University)
The press release…