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An X-ray structure of the surface spike of the Ebola virus could explain how this lethal pathogen infects human cells and may help researchers devise preventative measures to stop the virus spreading during an outbreak. You've got a one in two chance of surviving common infection with the incurable haemorrhagic fever known as Ebola, although for some strains the odds lengthen to one in ten. It is a particularly nasty pathogen with most deaths being due to a combination of dehydration, massive bleeding, and shock. Ebola is caused by certain members of the Filoviridae group of viruses. The viruses are long and filamentous and surrounded by a protein-lipid viral envelope. Fruit bats are thought to be the asymptomatic hosts that act as a reservoir for the virus. While the virus is currently ravaging gorilla populations in the central African lowlands, it is its lethality that means it is very unlikely to reach global epidemic proportions among people. Nevertheless, clues as to its structure could help medicine find ways of quashing outbreaks before there are too many fatalities. Using X-ray crystallography, Erica Ollmann Saphire, Dennis Burton, and colleagues at The Scripps Research Institute, La Jolla have determined the structure of the glycoprotein GP. GP is the only viral protein present on the surface of the Ebola virus particle. The researchers explain that their structure reveals several important features that offer clues as to how it attaches to cells prior to infection. The sample of GP protein used in the study was bound to a human neutralizing antibody from an outbreak survivor. The study was possible because of the discovery of an antibody isolated by Burton from bone marrow extracted from one of the few survivors of the 1995 Ebola outbreak in Kikwit, a city in the southwestern part of the Democratic Republic of Congo. The Kikwit outbreak was particularly lethal, having a greater than 90% mortality rate for those infected with the disease. By noting which parts of the virus interact with the antibody, the researchers were able to identify how antibodies might prevent the virus from infecting, thus protecting immune individuals from fatal disease. The insight could help researchers develop an antiviral therapy to prevent infection in those people who are susceptible to the disease. "Much about Ebola virus is still a mystery," says Erica Ollmann Saphire, the Scripps Research scientist who led the five-year effort working with Burton, and colleagues Jeffrey Lee, Marnie Fusco, Ann Hessell, and Wendelien Oswald, "However, this structure now reveals how this critical piece of the virus is assembled and, importantly, identifies vulnerable sites that we can exploit." The best that healthcare can currently offer is administering fluids for patients and isolating anyone infected. The work of Ollmann Saphire and her team opens a window on a more effective solution. The structure of the antibody together with the viral GP points to a mechanism underlying the assembly of the molecules on the viral surface, hints at how the viruses utilises a chemical "invisibility cloak". This could explain how the pathogen evades and exploits the human immune system. But, the structure gives researchers a helping hand for designing antiviral drugs or a vaccine against Ebola. "Structures of the native, oligomeric forms of viral glycoproteins as they exist on the viral surface are exceedingly difficult to achieve and thus exceedingly rare," notes Ollmann Saphire. "This structure now provides templates by which researchers studying other viruses could try to understand how their virus's surface protein is assembled and neutralized by an antibody." As such, the research could prove useful in the study of other viruses, such as Marburg, another member of the Filoviridae genus. Related links:
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