Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study builds dossier on JC polyomavirus

11.06.2013
The JC polyomavirus is clearly opportunistic. It infects half the population but lethally destroys brain tissue only in immunocompromised patients — and it may be outright sneaky, too.

Even as a new research paper allays fears that common mutant forms of the virus are the ones directly responsible for the disease's main attack, that same finding raises new questions about what the mutants are doing instead.


A JC Polyomavirus approaches a cell to bind with LSTc carbohydrates.

Credit: Ursula Neu/Tübingen University

Even if they are not the ones killing key brain cells, the mutants are up to some kind of no good, scientists suspect, because they are only found in the people who become sick with progressive multifocal leukoencephalopathy. PML sickens and usually kills one in 25 people with HIV-1 or one in 500 who receive a certain treatment for multiple sclerosis. The mutants appear plentiful in the blood and cerebral spinal fluid of sick patients, but in healthy carriers, the virus never mutates or spreads to the brain.

"The thinking in the field has been that these mutants possibly represent the pathogenic form of the virus," said Walter Atwood, a Brown University biologist and co-corresponding author on the new paper published June 11 in the journal mBio. "But there is no evidence that these things interact with the known receptors that are required for infection. This is the first report to show that, in fact, they are not infectious. But they may contribute to disease in ways we don't yet understand."

The mutant forms of the virus, the paper's authors from Brown University and University of Tübingen hypothesize, might provide a grand diversion to help the main virus evade the immune system, or they could be attacking different cells than the main virus does in an as yet undiscovered way.

Mutants not infectious

In the study, Atwood's team, led by co-first authors Melissa Maginnis of Brown and Luisa Ströh of Tübingen, looked at common mutant strains both in a series of lab experiments and through direct structural investigations using x-ray crystallography. What they determined is that the mutants are unable to bind at the virus's preferred site, a carbohydrate called LSTc, on the surface of both astrocytes and oligodendrocytes. Those two types of brain glial cells are the known targets of the virus. They produce myelin, a necessary sheathing for neurons, the message centers of the brain.

In the lab at Brown the researchers showed that the mutants are ostensibly harmless by infecting some glial cells with DNA from the virus's normal form and some with DNA from several common mutants and culturing them all for 22 days. Only the normal, or "wild-type," virus grew or spread at all.

Meanwhile the Tübingen scientists also resolved the crystal structures of three different mutant viruses and saw that even though the mutants overall had the same structure as the main virus, the sites at which they bind to LSTc all had local structural differences that either made binding impossible or much more difficult.

"It is a physical blocking," said Ströh, who is now visiting Brown from Tübingen as part of an exchange program. "Introducing one change can physically block, or at least partially block, interaction with LSTc, but the protein itself is still folded correctly."

To further rule out the chance that the mutant viruses could bind to and infect glial cells, the lab team then inserted normal and mutant polyomavirus proteins into pseudoviruses that could infect cells in culture even if they carried the mutations. Then they exposed several human brain cell types to the mutant and normal pseudoviruses. Only the pseudoviruses with normal DNA managed to infect the cells. The mutants still could not.

Mutant mystery

So what other role might the mutants play in attacking the brain? The study's authors offer two main possibilities, although there are others as well. (The researchers acknowledge that their experiments with glial cells in the lab are not exactly the same as tracking actual infection — or non-infection — in the brain).

Atwood's preferred hypothesis is that the mutants help the main form of the virus evade the patient's ailing immune system.

"It's not uncommon for viruses to accumulate mutations in their outer surfaces that alter antibody recognition," Atwood said. "These altered surfaces are attacked by the immune system. So the virus is spitting out a bunch of mutant viruses to serve as a smokescreen to the immune system as if to say, 'Attack all this garbage, but I can still go on to infect the next cell.'"

Another hypothesis, favored by Maginnis and Ströh, is that the mutants infect a different kind of cell in a way that does not require binding to LSTc.

"Perhaps they are infectious in endothelial cells," Maginnis said. "The lack of binding to LSTc might allow it to spread more freely. For example, the mutant viruses might be able to spread cell to cell in a mechanism that doesn't involve binding to receptors on the surface of cells, and perhaps this is how the virus crosses the blood-brain barrier."

Whether they are distracting and evading the immune system, slipping into other cells and sneaking through the blood-brain barrier, or something else, the mutants remain a serious concern to scientists, physicians, and patients, because JC polyomavirus remains a killer on the loose.

In addition to Maginnis, Ströh, and Atwood, other authors are Gretchen Gee, Bethany O'Hara, and Aaron Derdowski of Brown, and Thilo Stehle of Tübingen and Vanderbilt University.

The National Institute of Neurological Disorders and Stroke funded the research with grants 5P01NS065719 and F32NS064870.

David Orenstein | EurekAlert!
Further information:
http://www.brown.edu

More articles from Life Sciences:

nachricht Fine organic particles in the atmosphere are more often solid glass beads than liquid oil droplets
21.04.2017 | Max-Planck-Institut für Chemie

nachricht Study overturns seminal research about the developing nervous system
21.04.2017 | University of California - Los Angeles Health Sciences

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

Im Focus: Quantum-physical Model System

Computer-assisted methods aid Heidelberg physicists in reproducing experiment with ultracold atoms

Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...

Im Focus: Glacier bacteria’s contribution to carbon cycling

Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.

A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

New quantum liquid crystals may play role in future of computers

21.04.2017 | Physics and Astronomy

A promising target for kidney fibrosis

21.04.2017 | Health and Medicine

Light rays from a supernova bent by the curvature of space-time around a galaxy

21.04.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>