Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A step forward in virology

25.04.2008
Viruses use various tricks and disguises to invade cells. ETH Zurich researchers have now discovered yet another strategy used by viruses: the vaccinia virus disguises itself as cell waste, triggers the formation of evaginations in cells and is suspected to enter the cell interior before the immune defense even notices. The research results have been published in Science.

The vaccinia virus has a problem: it is a giant among viruses and needs a special strategy in order to infiltrate a cell and reproduce. Professor Ari Helenius and Postdoc Jason Mercer from ETH Zurich's Institute for Biochemistry have now discovered what this strategy is. In the process, they stumbled upon new and surprising findings.

The invasion strategy

In order to infiltrate a cell, the vaccinia virus exploits the cellular waste disposal mechanism. When a cell dies, other cells in the vicinity ingest the remains, without needing waste disposal experts such as macrophages. The cells recognize the waste via a special molecule, phosphatidylserine, which sits on the inner surface of the double membrane of cells. This special molecule is pushed out as soon as the cell dies and is broken into parts. The vaccinia virus itself also carries this official waste tag on its surface. "The substance accumulates on the shell of vaccinia viruses", Jason Mercer explained. The pathogen disguises itself as waste material and tricks cells into digesting it, just as they normally would with the remains of dead cells. As the immune response is simultaneously suppressed, the virus can be ingested as waste without being noticed.

The uptake into the cell itself is via macropinocytosis. The ETH Zurich researchers have demonstrated that the vaccinia virus moves along actin-rich filamentous extensions towards the cell. As soon as they impinge upon the cell membrane, an evagination forms, a bleb. The virus itself is the trigger for the formation of the evagination. Using a messenger substance to "knock on the door", the virus triggers a signaling chain reaction inside the cell so that the bleb forms, catches the virus and smuggles it into the cell.

Proteins as unsuspecting allies

"The viruses are the Trojan horses that want to enter Troy; the Trojans are the many proteins that transmit the signals and open the 'city gates' to the unwelcome guest", Ari Helenius said. Aided by Professor Lukas Pelkmans' team, Jason Mercer examined over 7000 different proteins in order to find out not only which Trojans let the virus in, but which as well are chiefly involved in the supply chain. Using definitive methods, the researchers de-activated each one of the suspected proteins to examine their function,and narrowed the vast number of proteins down to 140 potential culprits. The enzyme kinase PAK1 turned out to be an especially "helpful" citizen of Troy. Without PAK1, the pathogen's trick did not work and the cell did not form any evaginations.

Until now, very little has been known about the mechanism vaccinia viruses use to infiltrate a cell. Professor Helenius, whose research objective is to find out what methods and strategies various different viruses employ to invade somatic cells, clarified "This strategy is a new one". Other viruses, such as herpes, adeno and H1 viruses use macropinocytosis. However the vaccinia virus is the first one identified that uses apoptotic mimicry as an entry strategy.

Knowledge of the virus strategies and the signal proteins involved in the ingestion of a virus by a cell is crucial to finding and developing new agents against the pathogens. Until now, antiviral medication has targeted the virus itself. Ari Helenius, however, is looking for substances that interrupt the signaling chain and halt the communication between the virus and the cell. If the cell does not ingest a virus, the virus cannot reproduce and is quickly eliminated by the im-mune system. This process also has another big advantage: "Viruses cannot adapt to the obstruction of the signal chain all that quickly", he said.

further information:
ETH Zurich
Jason Mercer, Postdoctoral Fellow
Telephone +41 (0)44 632 58 18
jason.mercer@bc.biol.ethz.ch
*
Smallpox: a bioterrorist attack?
The vaccinia virus belongs to a family of particularly dangerous viruses, namely the pox viruses. The most infamous member, Variola, the casitive agent of smallpox constituted a global pandemic disease in the Middle Ages, causing the deaths of millions of people, especially among the indigenous population of North America who became infected by European settlers. Pox was the first viral disease against which a vaccination was developed. In 1771, the first rudimentary vaccine was produced from cowpox viruses, which protected people from the sequelae of the disease. Since 1978, the disease has been classed as eradicated and officially is preserved in only two laboratories; one in Atlanta, the other in Novosibirsk. US authorities, however, fear bioterrorist attacks with pox viruses. Research on these dangerous pathogens is thus encouraged.
*
ETH Zurich (Swiss Federal Institute of Technology Zurich) has a student body of nearly fourteen thousand students from 80 nations. About 360 professors teach mainly in engineering sciences and architecture, systems-oriented sciences, mathematics and natural sciences, as well as carry out research that is highly valued worldwide. Distinguished by the successes of 21 Nobel laureates, ETH Zurich is committed to providing its students with unparalleled education and outstanding leadership skills.

Renata Cosby | idw
Further information:
http://www.ethz.ch

Further reports about: Chain Helenius Mercer Pathogen Trojan evagination proteins vaccinia

More articles from Life Sciences:

nachricht In focus: Peptides, the “little brothers and sisters” of proteins
12.11.2018 | Technische Universität Berlin

nachricht How to produce fluorescent nanoparticles for medical applications in a nuclear reactor
09.11.2018 | Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB Prague)

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 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...

Im Focus: Coping with errors in the quantum age

Physicists at ETH Zurich demonstrate how errors that occur during the manipulation of quantum system can be monitored and corrected on the fly

The field of quantum computation has seen tremendous progress in recent years. Bit by bit, quantum devices start to challenge conventional computers, at least...

Im Focus: Nanorobots propel through the eye

Scientists developed specially coated nanometer-sized vehicles that can be actively moved through dense tissue like the vitreous of the eye. So far, the transport of nano-vehicles has only been demonstrated in model systems or biological fluids, but not in real tissue. The work was published in the journal Science Advances and constitutes one step further towards nanorobots becoming minimally-invasive tools for precisely delivering medicine to where it is needed.

Researchers of the “Micro, Nano and Molecular Systems” Lab at the Max Planck Institute for Intelligent Systems in Stuttgart, together with an international...

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

In focus: Peptides, the “little brothers and sisters” of proteins

12.11.2018 | Life Sciences

Materials scientist creates fabric alternative to batteries for wearable devices

12.11.2018 | Materials Sciences

A two-atom quantum duet

12.11.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>