Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Evolutionary 'battle scars' identify enhanced anti-viral activity

28.01.2008
Rapid evolution of a protein produced by an immunity gene is associated with increased antiviral activity in humans, a finding that suggests evolutionary biology and virology together can accelerate the discovery of viral-defense mechanisms, according to researchers at Fred Hutchinson Cancer Research Center.

These findings by Julie Kerns, Ph.D., a postdoctoral researcher in the Hutchinson Center’s Basic Sciences Division, published Jan. 25 in the open-access journal PLoS Genetics, present a striking example by which evolutionary studies can directly lead to biomedically important discoveries in the field of infectious diseases.

The immunity gene, called ZAP, is a key player in a newly discovered branch of antiviral defenses in mammals referred to as ‘‘intrinsic immunity.’’ Host proteins like ZAP can target intracellular stages of the viral life cycle to inhibit viral activity. The ZAP gene, first discovered in rats, thwarts a variety of divergent viruses, from retroviruses (like HIV) to alphaviruses (like Sindbis) to filoviruses (like Ebola).

Researchers believe ZAP functions by virtue of its RNA-binding abilities, which recognize specific sequences of the virus and target their viral RNA for destruction. Host-virus interactions are a classic example of genetic conflict in which both entities try to gain an evolutionary advantage over the other. This ‘‘back-and-forth’’ evolution is predicted to result in rapid changes of both host and viral proteins, which results in an evolutionary signature of positive selection, especially at the direct interaction interface.

“This suggests that we might be able to deduce host-virus conflicts purely by looking at rapidly evolving protein segments,” said Kerns, the lead author of the study, which was conducted in collaboration with senior author Harmit Singh Malik, Ph.D., of the Center’s Basic Sciences Division and co-author Michael Emerman, Ph.D., of the Center’s Human Biology Division.

The researchers found that there has been very little sequence evolution in the RNA-binding domain, which suggests that human ZAP may be similar to the rat gene in its viral RNA-binding specificity. However, surprisingly, the rapid evolution characteristic of “intrinsic immunity” genes was concentrated in a protein domain that was not even present in the originally discovered rat gene.

The authors found that humans encode two protein versions, or isoforms, from a single ZAP gene: a shorter version similar to the original rat gene and a longer version that possesses a rapidly evolving poly (ADP-ribose) polymerase (PARP)-like domain. In virological assays, the longer human ZAP protein isoform has higher antiviral activity. Thus, positive selection correctly predicted the more potent antiviral isoform of this protein.

The authors further suggest that ZAP is locked in a conflict with alphaviruses. The discovery of a potential human gene that can restrict alphaviral infection is particularly timely as the mosquito-borne alphavirus, Chikungunya, was responsible for a large epidemic in parts of Southeast Asia in 2006 and is now threatening to invade parts of Europe. The researchers believe this finding has important implications for the understanding of intrinsic immunity against viruses, and could potentially serve as a guide in the development of antiviral therapeutics.

“We think that a particular alphaviral protein may be playing an evolutionary ‘cat-and-mouse’ game with the ZAP gene,” Malik said. “Identifying this protein could lead to novel ways to tackle diseases caused by alphaviruses.”

Kristen Woodward | EurekAlert!
Further information:
http://www.fhcrc.org

Further reports about: Evolution Evolutionary Viral ZAP alphavirus antiviral immunity

More articles from Life Sciences:

nachricht Study shines light on brain cells that coordinate movement
26.06.2017 | University of Washington Health Sciences/UW Medicine

nachricht New insight into a central biological dogma on ion transport
26.06.2017 | Aarhus University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Study shines light on brain cells that coordinate movement

26.06.2017 | Life Sciences

Smooth propagation of spin waves using gold

26.06.2017 | Physics and Astronomy

Switchable DNA mini-machines store information

26.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>