Nav: Home

Transplant-damaging virus comes into focus

April 26, 2018

Researchers from the University of Leeds have revealed the structure of a virus which affects kidney and bone marrow transplant patients in near-atomic levels of detail for the first time.

This detailed information serves as a molecular-level structural visualisation, allowing scientists to study several potential targets for antiviral therapies or drugs.

In order to create a drug which can target viruses, researchers need to know what the virus looks like. With this knowledge, they can target chemical compounds at it in such a way that they bond with it precisely, stopping the virus from working. The more detailed the structure they have to work with, the more precision they can apply.

The research team at the University's Astbury Centre for Structural Molecular Biology focused on the infectious BK polyomavirus (BKV), using the centre's two cryo-electron microscopes to develop the incredibly detailed imaging required.

A research paper announcing the new structures has been published in the journal Structure. The level of detail in the image allows scientists to see features on the virus as tiny as ~3 Ångströms wide. One Ångström is equivalent to one ten-billionth of a metre or 0.1 nanometre. The structure is so small it cannot be seen by the naked eye.

Astbury Centre PhD researcher Dan Hurdiss, lead author of the paper, said: "Our structures provide the clearest picture to date of the infectious virus particle. This detailed information serves as a structural roadmap, allowing us to visualise several potential targets for antiviral therapies.

"These may include drugs which block BKV from entering our cells or which prevent proper assembly of the virus particle. Going forward, these structures may also be used to identify how antibodies from patients with other diseases recognise the BKV virus particle and thus aid in the development of a vaccine."

About 80% of the world's adult population is infected with BKV, but the virus rarely causes illness in people with a healthy immune system. However, in immunocompromised individuals, BKV can 'reactivate' and cause serious diseases.

Two such examples of BKV-associated diseases are polyomavirus-associated nephropathy (PVAN) and haemorrhagic cystitis (HC) which affect kidney and bone marrow transplant recipients respectively.

Around 10% of people who receive a kidney transplant will suffer from PVAN and up to 90% of these will go on to have their transplant organs rejected. At present, there are limited treatment options available for individuals suffering from BKV associated diseases.

The new structures will give hope to sufferers, by giving scientists a better-quality research tool to work with.

The structures were created using the cryo-electron microscopy method, by freezing infectious BKV particles and taking thousands of images using the microscopes. These two-dimensional images were then combined computationally to produce a high-resolution, three-dimensional view of the virus.

Professor Neil Ranson, Director of Cryo-Electron Microscopy at the University of Leeds, said: "Cryo-electron microscopy has been around for 30 years and has been incredibly useful, but until recently the technology lacked the ability to routinely look at molecules at the level of detail needed.

"Without that detail, scientists sometimes struggled to understand the structure of biological molecules and how they function, especially when they are in their normal workplace: inside our cells.

"However, the Titan Krios microscopes we have installed in Leeds are absolutely state-of-the-art, and mean that these limitations have been shattered. Researchers and industry users who work with us can now image biological molecules with an incredible resolution. Crucially, we'll also be able to see how these molecules interact with each other."
-end-
The BK Polyomavirus structure research was funded by Wellcome, Kidney Research UK and Kidney Research Yorkshire.

Further information

Journalists with questions or interview requests, or who would like to visit the University's cryo-electron microscopy suite should contact Peter Le Riche in the University of Leeds press office on 0113 343 2049 or email p.leriche@leeds.ac.uk

Photos and film footage of the microscopes is also available, as is a copy of the BK polyomavirus structure.

The DOI number of the research paper is DOI: 10.1016/j.str.2018.03.019, it will be live after the article is published 12.00pm EST / 5pm UK time on 26 April 2018.

University of Leeds

Related Virus Articles:

Smart virus
HSE University researchers have found microRNA molecules that are potentially capable of repressing the replication of human coronaviruses, including SARS-CoV-2.
COVID-19 - The virus and the vasculature
In severe cases of COVID-19, the infection can lead to obstruction of the blood vessels in the lung, heart and kidneys.
Lab-made virus mimics COVID-19 virus
Researchers at Washington University School of Medicine in St. Louis have created a virus in the lab that infects cells and interacts with antibodies just like the COVID-19 virus, but lacks the ability to cause severe disease.
Virus prevalence associated with habitat
Levels of virus infection in lobsters seem to be related to habitat and other species, new studies of Caribbean marine protected areas have shown.
Herpes virus decoded
The genome of the herpes simplex virus 1 was decoded using new methods.
A new biosensor for the COVID-19 virus
A team of researchers from Empa, ETH Zurich and Zurich University Hospital has succeeded in developing a novel sensor for detecting the new coronavirus.
How at risk are you of getting a virus on an airplane?
New 'CALM' model on passenger movement developed using Frontera supercomputer.
Virus multiplication in 3D
Vaccinia viruses serve as a vaccine against human smallpox and as the basis of new cancer therapies.
How the Zika virus can spread
The spread of infectious diseases such as Zika depends on many different factors.
Fighting the herpes virus
New insights into preventing herpes infections have been published in Nature Communications.
More Virus News and Virus Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: The Power Of Spaces
How do spaces shape the human experience? In what ways do our rooms, homes, and buildings give us meaning and purpose? This hour, TED speakers explore the power of the spaces we make and inhabit. Guests include architect Michael Murphy, musician David Byrne, artist Es Devlin, and architect Siamak Hariri.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at Radiolab.org/donate.     You can read The Transition Integrity Project's report here.