Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Single mutation gives virus new target

A mutation as minute as swapping just one amino acid can completely change the target that a virus will bind to on a victim cell — potentially shifting what kind of cell and eventually what kind of organism a virus could infect.

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.

Single switch
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!
Further information:

More articles from Life Sciences:

nachricht Sweetening neurotransmitter receptors and other neuronal proteins
28.10.2016 | Max-Planck-Institut für Hirnforschung

nachricht A new look at thyroid diseases
28.10.2016 | Jacobs University Bremen gGmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

A new look at thyroid diseases

28.10.2016 | Life Sciences

Sweetening neurotransmitter receptors and other neuronal proteins

28.10.2016 | Life Sciences

How nanoscience will improve our health and lives in the coming years

27.10.2016 | Materials Sciences

More VideoLinks >>>