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Viral Harpoon Structure Suggests Measles, HIV And Ebola Viruses Related

the order, or sequence, of amino acids that make up a protein – of many different paramyxovirus fusion protein molecules revealed that their basic structures are all similar.

But when the scientists analyzed the three-dimensional structure of the simian virus fusion protein, they were surprised to discover close structural similarities to fusion proteins from HIV, influenza and Ebola, said Lamb. Aside from this similarity, he said, "all these viruses have very different strategies for infecting cells and insinuating viral genetic material into the target cells to commandeer their machinery."

According to Lamb, the similarity among such widely varied viruses suggests that they might have had some common ancestor that shared a primitive version of the fusion protein. It is impossible at this point, however, to pinpoint the evolutionary origin of that ancestry, he said.

Regardless, said Lamb. "knowing the structure of this one fusion protein may lead to the development of drugs capable of thwarting the action of the fusion proteins of other members of the paramyxovirus family, and even possibly its distant viral cousins." At the least, he added, these findings will spur further studies involving other medically important viruses.

Specifically, determining the three-dimensional structure of the fusion protein sheds new light on the key event in paramyxovirus infection — when the virus unfolds itself to reveal a spikelike protein that is launched into the gel-like outer membrane of the target cell. "It's much like a harpoon going into a target," said Lamb.

He emphasized, however, that more research is needed to answer two important questions: What triggers the harpoon molecule to unfurl, and how does the fusion protein refold itself to draw the virus toward the ensnared target cell? "What happens there is a mystery," he said. "It's like spearing a shark. It’s relatively easy to spear it, but getting it onboard the boat
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
26-Mar-1999


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