Faculty of Biological Sciences

Research Bulletin

Viruses act like self-packing suitcases

17th October 2012

Faculty researchers have identified a crucial stage in the lifecycle of simple viruses like polio and the common cold that could open a new front in the war on viral disease.

Viruses act like self-packing suitcasestitle=The team are the first to observe at a single-molecule level how the genetic material (genome) that forms the core of a single-strand RNA virus particle packs itself into its outer shell of proteins. Lead researcher Professor Peter Stockley said their results overturn accepted thinking about the process and could open a chink in the armour of a wide range of viruses.

"If we can target this process, it could lead to a completely new class of anti-virals that would be less likely to create resistant viruses than existing drugs, which tend to target individual proteins," Professor Stockley said.

A number of important viruses like the common cold and polio have RNA (ribonucleic acid) instead of DNA as their genetic material. The observations reveal that the viruses' RNA initially has a much greater volume than the virus particles created after they are packed inside their protein shell.

"We realised that the RNA genome must have to be intricately folded to fit into the final container, just like when you pack to go on holiday and need to fold your clothes to fit into the space in your suitcase," said co-author Dr Roman Tuma from the University of Leeds' Faculty of Biological Sciences.

When the team added proteins to the viral RNA they saw an immediate collapse in its volume.

"It seems that viral RNAs have evolved a self-folding mechanism that makes closing the 'viral suitcase' very efficient. It's as though 'the suitcase and the clothes' work together to close the lid and protect the content," Dr Tuma said.

"The viral RNAs, and only the viral RNAs, can do this trick of folding up to fit as soon as they see the 'suitcase' coming. That's the important thing. If we can interfere in that process we've got a completely novel drug target in the lifecycle of viruses," Professor Stockley said.

"At the moment there are relatively few antiviral drugs and they tend to target enzymes that the virus encodes in its genome. The problem is that the drugs target one enzyme initially and, within the year, scientists are identifying strains that have become resistant. Individual proteins are extremely susceptible to this mutation. A fundamental process like the one we're looking at opens the possibility of targeting the collective behaviour of essential molecules, which could be much less susceptible to developing resistance," explained Professor Stockley.

The same phenomenon is seen in both bacterial and plant viruses. "While we have not proved it yet, I would put money on animal viruses showing the same mechanism too," Professor Stockley added.

The team used sophisticated instrumentation custom built at the University that allowed them to make the first ever single-molecule measurements of viral assembly. This allowed researchers to observe individual viral particles one at a time. "The specific collapse, which can only be seen in such assays, was totally unexpected and overturns the current thinking about assembly," Professor Stockley said.

The team also includes PhD student Alexander Borodavka, whose Wellcome Trust studentship funded the new research. They have recently secured a grant from the Biotechnology and Biological Sciences Research Council (BBSRC) to extend their research.

"We're now perfectly positioned to pursue questions about how this mechanism works in other viruses and we're already thinking about ways to start designing new antiviral drugs that would target this newly recognised feature of viral lifecycles," Professor Stockley said.

The research is published in the Proceedings of the National Academy of Sciences (PNAS).


Recent Grants

Dave Westhead and colleagues in Experimental Haematology, Cancer Research UK (Jan 2015), £700,521

Sheena Radford, Mark Harris, Peter Stockley, Alan Berry, Alex O'Neill, Thomas Edwards, Adrian Goldman, Anastasia Zhuravleva, Wellcome Trust (Jan 2015), £443,015

Bill Kunin, EU (Jan 2015), £157,490

John Colyer, Leeds Teaching Hospitals Charitable Fund (Jan 2015), £40,000

Chris Hassall, Royal Society (Dec 2014), £14,500

Ryan Seipke, Royal Society (Nov 2014), £13,700

Alan Berry, Wellcome Trust (Oct 2014), £749,865

Ian Hope, Marie-Anne Shaw, BBSRC (Oct 2014), £396,565

Alison Ashcroft, Peter Stckley, Sheena Radford, Nic Stonehouse, David Brockwell, Darren Tomlinson, BBSRC (Oct 2014), £340,937

Les Firbank, Joe Holden, BBSRC (Oct 2014), £210,302

Darren Tomlinson and colleagues in Chemistry and Pathology, anatomy and Tumour Biology, Dr Hadwen Trusy (Oct 2014), £194,475

Paul Knox, EU (Oct 2014), £167,229

Martin Stacey and colleagues in Medicine & Health, Pfizer (Oct 2014), £90,453

Darren Tomlinson and colleagues in Experimental Oncology, YCR (Oct 2014), £69,480

Andrew Macdonald, Jamel Mankouri, Kidney Research Fund UK (Oct 2014), £58,878

Mike McPherson and colleagues in Dentistry and Engineering, Wellcome Trust (Oct 2014), £58,437

Dave Westhead and colleagues in Experimental Haemotology, Leukaemia & Lymphoma Research (Sep 2014), £281,424

Emmanuel Paci and colleagues in Chemistry, BBSRC (Sep 2014), £636,759

Andrew Peel, BBSRC (Sep 2014), £371,598

Lars Jeuken, Stephen Evans, BBSRC (Sep 2014), £333,684

Lars Jeuken, BBSRC (Sep 2014), £313,463

Michelle Peckham, Mark Harris, Rao Sivaprasadarao, Eileen Ingham, Nic Stonehouse, Nikita Gamper, Wellcome Trust (Sep 2014), £192,763

Neil Ranson, BBSRC (Aug 2014), £355,253

Stuart Egginton, BHF (Aug 2014), £271,094

Darren Tomlinson, Mike McPherson, Technology Strategy Board (Aug 2014), £98,665

Peter Henderson, Leverhulme Trust (Aug 2014), £15,222

Mike McPherson (and colleagues in the School of Chemistry), EPSRC (Jul 2014), £819,880

Peter Stockley, Neil Ranson, BBSRC (Jul 2014), £455,787

Sheena Radford, Univesity of Michigan (Jul 2014), £138,452

Ryan Seipke, British Society Antimicrobial Chemistry (Jun 2014), £11,960

John Trinick, BHF (Jun 2014), £222,614

Chris West, Leverhulme Trust (Jun 2014), £181,241

Jon Lippiat, Darren Tomlinson, BBSRC (May 2014), £125,174

Christine Foyer, Royal Society (May 2014), £24,000

Recent
News

A bit of hot water can prevent the spread of invasive species

20th April 2015

When it comes to invasive species in the United Kingdom, a few ounces of hot water may be worth nearly £2 billion in annual management costs, according to a new study.


Parasite turns shrimp into voracious cannibals

18th March 2015

Parasites can play an important role in driving cannibalism, according to a new study.

 


New study on female fruit flies published by FBS Professor

17th March 2015

Female fruit flies may be more likely to reject the sperm of mates that are inferior, an international research team has found.


Uniting the women of science and engineering

10th March 2015

Three University of Leeds academics have been honoured with a Medical Research Council (MRC) Suffrage Award.


FBS Researchers volunteer to fight Ebola

17th February 2015

Four University of Leeds researchers have volunteered to fight the Ebola epidemic in Sierra Leone.


FBS Researchers discover viral code

4th February 2015

Researchers have cracked a code that governs infections by a major group of viruses including the common cold and polio.


Stroke damage mechanism identified

30th January 2015

FBS Researchers have discovered a mechanism linked to the brain damage often suffered by stroke victims—and are now searching for drugs to block it.


Impact
Stories

Professor Sheena Radford has undertook research to determine how peptides self-aggregate and form fibrils under certain conditions.

Professor John Altringham's research on the conservation of bat species has promoted the need for evidence based conservation practices

Professor Ian Chopra and Dr Alex O'Neill have shown that high levels of FA prevent the development of resistant bacteria.

Professor Eileen Ingham has led research over many years to develop improved approaches to aid healing and repair of soft tissues.

All impact stories