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.

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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

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

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

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

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

David Brockwell, Sheena Radford, Medimmune Ltd (Apr 2014), £337,661

Peter Stockley, Wellcome Trust (Apr 2014), £251,019

Mike McPherson, Wellcome Trust (Apr 2014), £146,596

Andrew Macdonald, Kidney Research Fund UK (Apr 2014), £127,237

Mike McPherson (and colleagues in School of Design), Technology Strategy Board (Apr 2014), £114,350

Paul Millner, Peter Stockley, Darren Tomlinson, YCR (Apr 2014), £95,874

Carrie Ferguson, Karen Birch, Shaunna Burke, Heart Research UK (Apr 2014), £60,140

Dave Westhead, MRC (Apr 2014), £18,304

Brendan Davies, BBSRC (Mar 2014), £451,829

Jim Deuchars, MRC (Mar 2014), £300,000

Adam Kupinski, Children with Cancer (Mar 2014), £50,000

Alison Baker, Steve Baldwin, BBSRC (Feb 2014), £403,439

Sarah Zylinski, BBSRC (Feb 2014), £355,869

Dave Lewis, Nigel Hooper, Tony Turner, Hugh Pearson, James Duce, Alzheimer's Society (Feb 2014), £29,871

Ronaldo Ichyama, Samit Chakrabarty, International Spinal Research Trust (Jan 2014), £304,600

Brendan Davies, BBSRC/Bayer Crop Science SA-NV (Jan 2014), £470,053

Adrian Goldman, Steve Baldwin, Stephen Muench, Thomas Edwards, Arwen Pearson , BBSRC (Jan 2014), £467,103

Stefan Kepinski, BBSRC (Jan 2014), £359,269

Elwyn Isaac, EU (Jan 2014), £179,445

Dave Westhead, Leukaemia & Lymphoma Research (Jan 2014), £105,937

John Barr, Thomas Edwards, MRC (Dec 2013), £469,505

Alex O'Neill, MRC (Dec 2013), £349,017

Darren Tomlinson, Yorkshire Cancer Research (Nov 2013), £142,334

Nikita Gamper, MRC (Nov 2013), £336,563

Keith Hamer, Alison Dunn, NERC (Nov 2013), £47,233

Alan Berry, Wellcome Trust (Oct 2013), £749,365

Urwin, Howard Atkinson, BBSRC (Oct 2013), £360,508

Eileen Ingham, Stacey-Paul Wilshaw, NHS R&D (Oct 2013), £356,623

Sheena Radford, BBSRC (Oct 2013), £329,906

Nigel Hooper, Alzheimer's Research (Oct 2013), £327,075

Eileen Ingham, EPSRC (Oct 2013), £276,751

David Beech, BHF (Oct 2013), £109,974

Mark Harris, Medical Research Foundation (Oct 2013), £34,455

James Dachtler, Royal Society (Oct 2013), £15,000

Ade Whitehouse, Teresa Rosenbaum Golden Charitable Trust (Oct 2013), £10,000

Jurgen Denecke, BBSRC (Sep 2013), £382,093

Andy Cuming, EU (Sep 2013), £257,714

Paul Knox, BBSRC (Sep 2013), £411,948

Vas Ponnambalam, Leverhulme Trust (Sep 2013), £245,031

Peter Meyer, EU (Sep 2013), £242,166

Dave Rowlands, Nic Stonehouse, EU (Sep 2013), £202,556

Derek Steele, BHF (Sep 2013), £103,629

Joan Boyes, NC3Rs (Sep 2013), £90,000

Peter Stockley, Royal Society (Sep 2013), £11,400

Darren Tomlinson, Leverhulme Trust (Sep 2013), £5,645

Nic Stonehouse, Dave Rowlands, BBSRC (Aug 2013), £574,906

Eileen Ingham, Wellcome Trust (Aug 2013), £191,470

Adrian Goldman, Royal Society (Aug 2013), £75,000

Mike McPherson, Wellcome Trust (Aug 2013), £40,000

Alison Ashcroft, Sheena Radford, Peter Henderson, BBSRC (Jul 2013), £462,248

Stacey-Paul Wilshaw, Wellcome Trust (Jul 2013), £180,690

Sheena Radford, US National Institutes of Health (Jul 2013), £161,866

Eileen Ingham, Wellcome Trust (Jul 2013), £95,261

Dave Lewis, Higher Education Academy (Jul 2013), £6,178

Alex O'Neill, EU (Jun 2013), £471,718

Andrew Macdonald, Breast Cancer Campaign (Jun 2013), £19,952

John Altringham, DEFRA Dept for Env. Food & Rural Affairs (May 2013), £127,945

Sheena Radford, EU (May 2013), £2,032,465

Michelle Peckham, Gareth Howell, Roman Tuma, David Beech, Nigel Hooper, MRC (May 2013), £893,675

Sarah Calaghan, Derek Steele, BHF (May 2013), £208,005

Andrew Peel, EU (May 2013), £79,147

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