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 Discovery of a Key Regulatory Gene in Cardiac Valve Formation
24.05.2017 | Universität Basel

nachricht Carcinogenic soot particles from GDI engines
24.05.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

Innovation 4.0: Shaping a humane fourth industrial revolution

17.05.2017 | Event News

 
Latest News

Information integration and artificial intelligence for better diagnosis and therapy decisions

24.05.2017 | Information Technology

CRTD receives 1.56 Mill. Euro BMBF-funding for retinal disease research

24.05.2017 | Awards Funding

Devils Hole: Ancient Traces of Climate History

24.05.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>