Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Single mutation gives virus new target

22.10.2013
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:
http://www.brown.edu

More articles from Life Sciences:

nachricht Immune Defense Without Collateral Damage
23.01.2017 | Universität Basel

nachricht The interactome of infected neural cells reveals new therapeutic targets for Zika
23.01.2017 | D'Or Institute for Research and Education

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Tracking movement of immune cells identifies key first steps in inflammatory arthritis

23.01.2017 | Health and Medicine

Electrocatalysis can advance green transition

23.01.2017 | Physics and Astronomy

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>