Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers Uncover How Poxviruses Such as Smallpox Evolve Rapidly -- Despite Low Mutation Rates

20.08.2012
Poxviruses, a group of DNA-containing viruses that includes smallpox, are responsible for a wide range of diseases in humans and animals. They are highly virulent and able to cross species barriers, yet how they do so has been largely a mystery because of their low mutation rates.

While smallpox was considered officially eradicated by the World Health Organization in 1980, concerns about its use as a bioterrorism agent – and the finding that other poxviruses, such as monkeypox, can be transmitted from animals to humans – have spurred renewed interest in understanding how they replicate. Having this information in hand could lead to the development of better antiviral strategies.

New research from scientists at Fred Hutchinson Cancer Research Center and collaborating institutions has uncovered how poxviruses evolve to rapidly adapt against host defenses – despite their low mutation rates.

The discovery provides new insight into how large, double-stranded DNA viruses evade host immunity and become drug resistant, and it has particular implications for understanding the mechanisms of infectious-disease transmission between animals and humans.

Senior author Harmit S. Malik, Ph.D., a member of the Hutchinson Center’s Basic Sciences Division, and first author Nels C. Elde, Ph.D., a former postdoctoral researcher in Malik’s lab, describe their findings online ahead of the Aug. 17 print issue of Cell.

“Poxviruses encode a variety of genes that help them to counter host immune defenses and promote infection,” said Elde, now an assistant professor of human genetics at the University of Utah School of Medicine. “Despite ample evidence that the poxvirus genome can undergo adaptive changes to overcome evolving host defenses, we still don’t know that much about the mechanisms involved in that adaptation.”

To determine the mechanisms of adaptation, Elde, Malik and colleagues conducted an experiment in cell culture using vaccinia virus, the type of poxvirus used in the smallpox vaccine, to mimic viral adaptation and evolution as it occurs in nature.

Previous research had demonstrated that a host-defense protein called protein kinase R (PKR) is a major hurdle to poxvirus infection. In response, poxviruses have evolved to overcome PKR by encoding two genes, K3L and E3L, which thwart host-defense mechanisms that normally prevent viral infection.

The team studied how vaccinia virus, when altered to delete the E3L gene, evolved to successfully replicate in the presence of human PKR.

“Dramatically, serial propagation of this ‘weaker’ virus rapidly resulted in strains that became much more successful at replicating in human cells,” said Malik, who is also an Early Career Scientist of the Howard Hughes Medical Institute.

Closer examination of their mode of adaptation revealed that the virus was quickly able to defeat PKR by selectively increasing the number of copies of the K3L gene in its genome.

Malik likened this rapid adaptation to the expansion of the bellows of a musical accordion. “As the K3L copy number increased in subsequent rounds of replication, so did expression of the K3L protein and subsequent inhibition of the immune response,” he said. This showed that viruses that can quickly expand their genome have an immediate evolutionary advantage over those that cannot.

In a further extension of the accordion analogy, in addition to observing rapid gene expansion in the E3L-deficient strain of vaccinia, the researchers also observed that the virus contracted after acquiring an adaptive mutation, swapping a beneficial mutation for a smaller genomic footprint.

“Our studies suggest that despite their transient nature, gene expansions may provide a potent means of adaptation in poxviruses, allowing them to survive either immune or pharmacological challenges,” Malik said. “Recognizing the means by which they undergo this expansion may provide more effective antiviral strategies against these and related important pathogens.”

The National Institutes of Health, the National Science Foundation, the Howard Hughes Medical Institute and the Life Sciences Research Foundation funded the research. In addition to researchers at the Hutchinson Center and University of Utah School of Medicine, the study also involved collaborators at the University of Washington School of Medicine.

Note for media only: To obtain a copy of the Cell paper, “Poxviruses deploy genomic accordions to adapt rapidly against host antiviral defenses,” please visit press@cell.com.

At Fred Hutchinson Cancer Research Center, our interdisciplinary teams of world-renowned scientists and humanitarians work together to prevent, diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers, including three Nobel laureates, bring a relentless pursuit and passion for health, knowledge and hope to their work and to the world. For more information, please visit www.fhcrc.org.

Kristen Woodward | Newswise Science News
Further information:
http://www.fhcrc.org

More articles from Life Sciences:

nachricht Colorectal cancer risk factors decrypted
13.07.2018 | Max-Planck-Institut für Stoffwechselforschung

nachricht Algae Have Land Genes
13.07.2018 | Julius-Maximilians-Universität Würzburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Research finds new molecular structures in boron-based nanoclusters

13.07.2018 | Materials Sciences

Algae Have Land Genes

13.07.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>