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Biologists visualize protein interaction that may initiate viral infection

ly one of the first lines of defense in the immune system," Kuhn said. "The first step in a virus infecting a cell is usually the attachment of the virus to the receptor. That's essentially what we are looking at, except in this case, instead of having the receptor, which is normally bound or attached to the cell, we have just a portion of the receptor, the CRD, which we produced separately."

Dengue belongs to a family of viruses known as flaviviruses, which includes a number of dangerous insect-borne diseases such as West Nile, yellow fever and St. Louis encephalitis. These diseases, however, use different biological mechanisms than dengue to infect host cells. Dengue is prevalent in Southeast Asia, Central America and South America. Mosquitoes transmit the virus to people, setting in motion the infection process.

"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. "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 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 .
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Source:Purdue University


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