Ebola and its equally gruesome cousin, Marburg, have played starring roles in best-selling books and Hollywood movies. But how these terrifying viruses work is largely unknown. Now researchers have uncovered an intriguing lead: The folate receptor-a (FR-a), a molecule found on the surface of many cell types, helps both viruses infect cells.
Many viruses cause infections by first docking onto receptors on cell surfaces. But the researchers, led by Mark Goldsmith at the Gladstone Institute of Virology and Immunology in San Francisco, carefully avoid calling FR-a a "receptor" for Ebola and Marburg. Rather, they describe it as a "cofactor for cellular entry"--which is another way of saying that they don't yet know the precise role that FR-a plays in opening the cellular door to these invaders.
The Gladstone researchers knew that Ebola and Marburg do not infect T cells. These cells thus provide an ideal system for testing, one by one, possible factors that allow the viruses to enter other kinds of cells. The researchers engineered new T cells to contain one or more genes from vulnerable cells, and then they checked whether they could infect them with chimeric viruses that combined a surface protein from Marburg or Ebola with HIV. (Researchers routinely use such "pseudotype" viruses of both Marburg and Ebola because few labs have the biosafety capabilities to work with the real pathogens.)
The team reports in this week's issue of Cell that the strategy worked only if the T cells were given the gene for FR-a Working with Alan Schmaljohn at the U.S. Army Medical Research Institute of Infectious Diseases in Fort Detrick, Maryland--which has one of two labs in the United States equipped to handle the hottest viruses--the researchers also demonstrated that wild-type Marburg virus could infect T cells only if they were modified to contain FR-a.
Several caveats remain. Rather than serving as a receptor for Ebola and Marburg, FR-a might send signals that tell the cell to let the viruses enter, says Ebola researcher Gary Nabel, who heads the Vaccine Research Center at the National Institutes of Health. Even so, "it's an important finding," says Paul Bates of the University of Pennsylvania in Philadelphia. If FR-a does turn out to be a crucial accomplice for viral entry, this insight might point the way to novel treatment and vaccine strategies.