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 suitcasesThe 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

Neil Ranson, Mark Harris, Ade Whitehouse, Peter Stockley, Sheena Radford, Alan Berry, Wellcome Trust (Mar 2016), £1,000,000

Katie Field, BBSRC (Jan 2016), £830,381

Alan Berry, Alex Breeze, Adam Nelson, BBSRC (Jan 2016), £479,490

Alan Berry, Wellcome Trust (Oct 2015), £752,365

Julie Aspden, MRC (Oct 2015), £633,020

Steve Sait, NERC (Oct 2015), £386,061

Urwin, Howard Atkinson, BBSRC (Oct 2015), £200,293

Eric Hewitt, Andrew Macdonald, Yorkshire Kidney Research Fund (Oct 2015), £46,621

Ade Whitehouse, Alison Ashcroft, Ian Carr, BBSRC (Sep 2015), £438,975

Dave Westhead, Leukaemia & Lymphoma Research Leukaemia & Lymphoma Research (Sep 2015), £430,567

Shaunna Burke, Andrea Utley, Sarah Astill, Arts Council of England (Sep 2015), £80,594

Samit Chakrabarty, Ronaldo Ichiyama, Intl Foundn for Research in Paraplegia (Aug 2015), £93,000

Eileen Ingham, John Fisher, EPSRC (Jul 2015), £1,458,439

Anastasia Zhuravleva, BBSRC (Jul 2015), £483,019

Alex O'Neill, MRC (Jul 2015), £249,822

Ade Whitehouse, Richard Foster, Cancer Research UK (Jul 2015), £201,034

Ronaldo Ichiyama, Jim Deuchars, Sue Deuchars, Wings For Life Spinal Cord Research (Jul 2015), £123,895

Helen Miller, ABNA Ltd (Jul 2015), £22,968

Martin Stacey and colleagues in FMH, MRC (Jun 2015), £426,475

Adrian Goldman, Sarah Harris, Roman Tuma, BBSRC (Jun 2015), £420,693

Elwyn Isaac, EU (Jun 2015), £238,915

Christine Foyer, BBSRC (Jun 2015), £160,401

Adrian Goldman, EU (Jun 2015), £116,331

David Brockwell, Sheena Radford, Innovate UK (Jun 2015), £113,378

Yoselin Benitez-Alfonso, EPSRC (Jun 2015), £93,672

Michelle Peckham, Peter Knight, Thomas Edwards, BBSRC (May 2015), £404,987

Michelle Peckham, Ed White, Peter Knight, BHF (May 2015), £208,184

Dave Westhead, Sheena Radford, Alex Breeze, BBSRC (May 2015), £51,021

Steve Clapcote, Vitaflo International Ltd (May 2015), £33,703

Les Firbank, Joe Holden, Pippa Chapman, NERC (Apr 2015), £388,726

Samit Chakrabarty, David Steenson, BBSRC (Apr 2015), £120,103

Paul Millner, Gin Jose, Sarah Aickin, DSTL Porton Down (Apr 2015), £63,407

Chris Hassell, David Lewis, The Physiological Society (Apr 2015), £6,900

Andrew Tuplin, Royal Society (Mar 2015), £15,000

Yoselin Benitez-Alfonso, Royal Society (Mar 2015), £14,770

Patricija Van Oosten-Hawle, Royal Society (Mar 2015), £13,960

Stuart Egginton, BHF (Mar 2015), £272,979

Keith Hamer, Department of Energy & Climate Change (Mar 2015), £58,066

Andrew Macdonald, Yorkshire Kidney Research Fund (Mar 2015), £41,171

Les Firbank, DEFRA Dept for Env. Food & Rural Affairs (Feb 2015), £20,000

Ian Hope, Marie-Anne Shaw, BBSRC (Jan 2015), £381,998

Paul Knox, BBSRC (Jan 2015), £5,000

Andrew Peel, BBSRC (Jan 2015), £359,077

Christine Foyer, BBSRC (Jan 2015), £408,334

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

Mike McPherson, Christoph Walti, DSTL Porton Down (Jan 2015), £625,125

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

Alison Ashcroft, Peter Stockley, Sheena Radford, Nicola Stonehouse, David Brockwell, Darren Tomlinson, BBSRC (Jan 2015), £340,937

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

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


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