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 Microscope measures muscle weakness
16.11.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

nachricht Good preparation is half the digestion
16.11.2018 | Max-Planck-Institut für Stoffwechselforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: UNH scientists help provide first-ever views of elusive energy explosion

Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.

Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

European Space Talks: Weltraumschrott – eine Gefahr für die Gesellschaft?

23.10.2018 | Event News

 
Latest News

Purdue cancer identity technology makes it easier to find a tumor's 'address'

16.11.2018 | Health and Medicine

Good preparation is half the digestion

16.11.2018 | Life Sciences

Microscope measures muscle weakness

16.11.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>