3-D images reveal key step in viral entry into cells
Findings could yield treatment approaches for dengue, West Nile, hepatitis C, and other viruses
Work published in the Jan. 22, 2004, issue of Nature is a significant advance in the understanding of how viruses cause infection, and offers two possible strategies for blocking these infections with antiviral drugs or vaccines. The research involved a major category of viruses known as “enveloped” viruses, so called because of their fatty outer membrane. Class 1 enveloped viruses include influenza and HIV; the new research focuses on class 2 enveloped viruses, responsible for causing dengue fever, West Nile fever, hepatitis C, tick-borne encephalitis, Japanese encephalitis, and other lesser-known diseases. “Many of these are emerging infections,” notes Stephen Harrison, a Howard Hughes Medical Institute investigator and chief of the laboratory of molecular medicine at Children’s Hospital, who was the senior investigator on the study. Led by Yorgo Modis, a structural biologist and postdoctoral fellow in Harrison’s laboratory at Children’s Hospital, the researchers used X-ray crystallography to study a key envelope protein that sits on the membrane of the dengue virus. By aiming an X-ray beam through a crystallized form of the protein, they obtained three-dimensional images, precise down to the atom, showing how a shape change in the protein causes fusion to happen.