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
Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München
Second research flight into zero gravity
21.10.2016 | Universität Zürich
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.
Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
21.10.2016 | Health and Medicine
21.10.2016 | Information Technology
21.10.2016 | Materials Sciences