Scientists at The Scripps Research Institute (TSRI) have discovered the molecular mechanism by which the deadly Ebola virus assembles, and what they discovered comes as a surprise: SHAPE SHIFTING! The same molecule that assembles and releases new viruses also rearranges itself into different shapes, with each shape controlling a different step of the virus’s life cycle.
The newly discovered “shape-shifting” or “transformer” behavior of Ebola explains how the virus can control a multi-step viral lifecycle using a limited number of genes. More importantly, insight from the TSRI study means that new drugs to block viral replication could target any of the structures themselves or the intermediate steps in the structural transformation process.
The finding revises a central dogma of molecular biology: That a protein molecule has one shape that predestines one biological function.
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| Viral Multiplication |
“These findings open doors to developing new drugs against Ebola,” adds Zachary Bornholdt, PhD, senior staff scientist and first author of the study.
“Drugs to block viral replication could target any of the structures themselves or the intermediate steps in the structural transformation process.”
Ebola hemorrhagic fever is one of the most virulent diseases known to humankind. Very few pathogens prove more dangerous than Ebola virus once a person is infected. There is no cure, and the case-fatality rate can be up to 90 percent, depending on which strain is involved.
Ebola virus and its cousin Marburg virus are spread when people come into contact with the bodily fluids of a person or animal who is already infected. Infection causes rapidly progressing high fever, hemorrhage and shock. No drugs or vaccines are yet available for human use. Currently, the standard treatment consists of administering fluids and taking protective measures to ensure containment, such as isolating the patient and washing sheets with bleach.
Once rare, the viruses are now reemerging with increasing frequency, and have caused at least four outbreaks among humans in the last two years. Although the viruses are found most often in Africa, they have been unintentionally imported into the United States and Europe several times, and in recent years a version of the Ebola virus has been found replicating in swine raised for human consumption in Asia.
To conduct the study, Saphire and her group at TSRI collaborated with Yoshihiro Kawaoka, PhD, DVM, who holds joint appointments at the University of Wisconsin and University of Tokyo. Kawaoka’s group provided cellular microscopy and critical replication experiments to complement the TSRI team’s expertise in x-ray crystallography and protein biochemistry.
Findings appear in the journal
Contributing sources:
Ebola virus assembly yields a big surprise | La Jolla Light:
Scientists reveal how deadly Ebola virus assenbles
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