Adenoviruses cause numerous diseases, such as eye or respiratory infections, and they are widely used in gene therapy. Researchers from the University of Zurich have now discovered how these viruses penetrate the cells, a key step for infection and gene delivery The cell unwillingly supports virus entry and infection by providing lipids that are normally used to repair damaged membranes.
An intact cell membrane is essential for any cell to function. The external cell membrane can be damaged by mechanical stress, for example in muscle cells, or by pathogens, such as viruses and bacteria. Membrane damage can result in small pores, which lead to loss of valuable substances from the cell.
The cell can quickly repair such injuries to its membrane. Human adenoviruses also cause small pores in the cell membrane, as a team of cell biologists headed by Urs Greber, a professor at the Institute of Molecular Life Sciences at the University of Zurich, has now discovered.
These pores are too small for the virus to get directly into the cell but are large enough for the cell to recognize them as a danger signal and repair them in a matter of seconds. The adenovirus uses this very repair mechanism to trigger an infection.
Certain lipids help the virus to enter the cell
During this repair process, lipids – in particular ceramide lipids – are formed, which enable the virus to enter the cell more rapidly. The ceramide lipids cause the membrane to bend and endosomes to form.
Endosomes are small bubbles of lipids and proteins and they engulf extracellular material, such as nutrients, but also viruses. With the aid of the ceramide lipids, the virus increases the size of the membrane lesions, and can leave the endosome before the endosome becomes a lysosome and degrades the virus.
The virus then multiplies in the nucleus and subsequently infects other cells. “We have identified particular cellular lipids as key components for the virus to enter into cells, which is surprising as lipids have important roles in biology, but these roles are difficult to identify,” explains Stefania Luisoni, the first author on the study and a doctoral student at the Institute of Molecular Life Sciences.
The scientists identified a connection between the formation of a membrane pore by the virus and a cellular repair mechanism. These events form a positive feedback loop, which is part of the explanation for the high infection efficiency of the adenoviruses, which scientists have known for some time.
The work also identified a new inhibitor against the adenoviruses, which inhibits the cellular protein “lysosomal acid sphingomyelinase“, and blocks the formation of ceramide lipids in the plasma membrane. “Our results are potentially interesting for the development of new anti-viral agents, and they increase our understanding in how the adenovirus works in vaccination and gene therapy” concludes Greber.
Stefania Luisoni, Maarit Suomalainen, Karin Boucke, Lukas B. Tanner, Markus R. Wenk, Xue Li Guan, Michal Grzybek, Ünal Coskun, Urs F. Greber. Co-option of Membrane Wounding Enables Virus
Penetration into Cells. Cell Host & Microbe, July 8, 2015. http://www.sciencedirect.com/science/article/pii/S1931312815002541
Nathalie Huber | Universität Zürich
Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care
Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
17.11.2017 | Physics and Astronomy
17.11.2017 | Health and Medicine
17.11.2017 | Studies and Analyses