Manipulated Porter: How do viruses get into the nucleus

Adenoviruses trigger respiratory problems and are dangerous to humans than previously thought. Porter molecules and manipulate them to penetrate through the host cell into the cell nucleus. A research team led by cell biologist and virologist at the University of Zurich was able to present evidence of this mechanism in detail.

You are a successful model of evolution, and it exists since time immemorial: Viruses. Viruses are extremely adaptable, but they have a problem: you can not replicate themselves but inject their genes into a suitable host cell. Some viruses must reach the viral DNA for replication in the cell nucleus. It has been known for almost 50 years. We know, for example, that the adenovirus to stores in a first step, its protein coat. But how and why the DNA is revealed and smuggles himself into the host cell, remained unanswered despite decades of research.

Now it is a research group headed by Urs Greber, cell biologist at the University of Zurich managed to clarify these points. As the scientists show recently in the magazine "Cell Host & Microbe," viruses use the cell's own mechanisms. The virus attaches itself to a porter molecule, which sits at the nuclear pore complex in the nuclear membrane and controls access into and out of the nucleus. Another protein of the nuclear pore complex binds to and activates a motor protein of kinesin family, which regulates the transport of materials in the vicinity of the nucleus.

Viral DNA is revealed with the help of the host cell

"The motor protein is in an activated state, can bind to microtubules and move along microtubules," says Professor Greber, the observations of his team. And exactly this situation, the virus uses docked for his purposes. The virus binds to the kinesin-like this and uses the energy of the engine to tear your own envelope. The viral DNA becomes exposed and is ready for transport to the nucleus. The action of the activated motor has another effect: the plant nuclear pore to tears and is increased significantly. This viral DNA enters more easily into the cell nucleus. Amazingly, the cell repairs the defective nuclear pore, allowing the virus seems to break into the core leaving no damage. The viral DNA is introduced almost without trace in the core and can be easily reproduced there.

For their investigations, researchers used the adenoviruses. Adenoviruses trigger respiratory diseases including eye infections or epidemic. They were regarded until recently as a relatively harmless to healthy people. Research results of another group, however, have recently shown that a novel adenovirus caused a dreaded zoonotic disease. It was thus transferred from one animal to humans and then spread from person to person.

Publication:  Sten flugs, Martin F. Engelke, I-Hsuan Wang, Daniel Punter, Karin Boucke, Sibylle Schleich, Michael Way, Philip Schoenberger, Christoph J. Burckhardt, and Urs F. Greber: Kinesin-1-mediated capsid disassembly and disruption of the Nuclear Pore ​​Complex Promote virus infection, in: Cell Host & Microbe 10, 15 September 2011, DOI: 10.1016/j.chom.2011.08.010

Source: University of Zurich