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:
Renata Cosby | idw
Designer cells: artificial enzyme can activate a gene switch
22.05.2018 | Universität Basel
Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.
The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
23.05.2018 | Physics and Astronomy
23.05.2018 | Agricultural and Forestry Science
23.05.2018 | Physics and Astronomy