In a new study published online in the journal PLoS Pathogens, an international team of scientists showed that by swapping a single amino acid they could change the sugar to which the human BK polyomavirus will binds on the surface of cells. The BK polyomavirus lost the ability to bind its usual target sugar and instead “preferred” the same sugar as its cousin SV40 polyomavirus, which is active in monkeys.
The binding sites on the surface of the BK polyomavirus, called capsomers, each have five monomers. Scientists found that changing just one amino acid in these monomers caused the virus to bind to an entirely different receptor on targeted cells than before. Credit: Atwood lab/Brown University
The researchers were working in cell cultures with safe pseudoviruses, which cannot spread, so they did not show that the pseudovirus changed its infectivity from one species to another, but the finding provides a novel demonstration of how easily the binding target of a virus can change as its structure mutates and evolves.
Different cells have different bindings targets on their surfaces. A change in a virus’s binding target preference can be a key step in changing how that virus would affect different cells in a victim — or move on to a different species.
“I think it’s one of the first, if not the first, times that a receptor switch of this nature has been identified,” said Brown University virologist Walter Atwood, a corresponding author of the paper published Oct. 10, 2013. “There are dozens of viruses that use these kinds of sugars as receptors. What we’re showing is that it doesn’t take much to convert from using one type of sugar to using another type of sugar. It helps us to understand evolutionarily how these viruses may adapt to a new host.”
Brown postdoctoral researcher Stacy-ann Allen, one of two lead authors on the paper, said the team learned of the single amino acid difference by comparing high-resolution structural models of the two polyomaviruses bound to their favorite sugars. Collaborators, including co-lead author Ursula Neu and co-correspondng author Thilo Stehle at the University of Tübingen in Germany, produced those models using nuclear magnetic resonance spectroscopy.
“We had the structures and sequences of both BK and SV40, and they are relatively similar in their amino acid identity,” Allen said. “So when you see minute differences between them, you can target these differences to ask whether this difference allows for different infection in different hosts.”
Sure enough, when Allen made the change at amino acid site 68 in the BK polyomavirus, it switched from binding the “ganglioside” sugar GD3 to binding with GM1.
Allen and colleagues tested this not only in cells in the lab, but also by dropping the viruses onto microarrays of binding target sugars.
And for even more confirmation, the Brown scientists sent the mutated BK viruses back to Germany for more NMR resolution.
“The NMR spectrum of the BK and the SV40 were identical,” Atwood said, “They thought they had mixed up the samples. They were identical in terms of their ability to bind to GM1, the monkey receptor.”
It may take several steps beyond a switch of receptor preference for a virus to infect new cells in the body or entirely new species, but such a switch could be a key step in more viruses than just the polyomavirus family, the scientists said. Others seem to switch preferences fairly quickly.
“Prominent examples include different serotypes of adenoviruses, the canine and feline paroviruses, as well as avian, swine, and human influenza viruses,” they wrote in PLoS Pathogens.
In addition to Atwood, Allen, Neu, and Stihle, other authors on the paper are Barbel Blaum and Luisa Stroh of Tübingen; Yan Liu, Angelina Palma and Ten Fiezi of Imperial College London; Martin Frank of Biognos in Sweden; and Thomas Peters of the University of Lübeck in Germany.
The study’s funding came from the National Institutes of Health (grants: 5R01CA71878-13, P01-NS065719), the Wellcome Trust (WT093378MA, WT099197MA), and the UK Research Council (GRS/79268, EP/G037604/1).
Editors: Brown University has a fiber link television studio available for domestic and international live and taped interviews, and maintains an ISDN line for radio interviews. For more information, call (401) 863-2476.
David Orenstein | EurekAlert!
North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich
Researchers Discover New Anti-Cancer Protein
22.03.2018 | Universität Basel
An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.
The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...
In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.
Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...
Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.
They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...
A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...
For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.
In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...
19.03.2018 | Event News
16.03.2018 | Event News
13.03.2018 | Event News
22.03.2018 | Materials Sciences
22.03.2018 | Health and Medicine
22.03.2018 | Earth Sciences