Viruses act like 'self-packing suitcases'

Oct 18, 2012

Researchers at the University of Leeds 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.

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 particle packs itself into its 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 () instead of DNA as their . The observations reveal that the viruses' RNA initially has a much greater volume than the created after they are packed inside their protein shell.

"We realised that the 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 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 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).

Explore further: Two-armed control of ATR, a master regulator of the DNA damage checkpoint

More information: Alexander Borodavska, Roman Tuma, and Peter G. Stockley, Evidence that viral RNAs have evolved for efficient, two-stage packaging, is published in Proceedings of National Academy of Sciences. (2012), vol 109, 15769–15774.

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TheKnowItAll
not rated yet Oct 18, 2012
I wouldn't be surprised if one day some scientists discovered that viruses are an integral part of genetic evolution, that said I would probably still take the treatment for the common cold if it came along. lol
Tausch
1 / 5 (1) Oct 18, 2012
A folding process?
Like proteins?
Torbjorn_Larsson_OM
5 / 5 (1) Oct 19, 2012
That a parasite like viruses would evolve amazing life style adaptations is rather the norm.

@ TheKnowItAll:

In the sense you mean they are part of cellular evolution, parasites puts selection pressure on other species and their ability to transport genes (horisontal gene transfer) acts as variation.

But some of them were also early divergent from the DNA LUCA before the 3 usual clades. At least the giant DNA viruses constitute a 4th universal tree clade in some phylogenetic methods. [ "Giant viruses coexisted with the cellular ancestors and represent a distinct supergroup along with superkingdoms Archaea, Bacteria and Eukarya", Nasir et al, 2012]

@ Tausch:

RNA has folds analogous to the primary fold structure of proteins, which is why they can act as ribozymes at times. [ http://en.wikiped...wiki/RNA , especially 1st ill.]

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