Phagocytes as accomplices of viruses

Epithelial cells are effectively protected from disease-causing germs. Still, it manages various viruses such as HIV, invade unknown way through the mucosa into the body. Cell biologists at the University of Zurich have now developed a new infection mechanism identified. They demonstrate that viruses use the body's scavenger cells to the infection. The new findings are for cancer gene therapy and the development of anti-viral drugs is important.

Epithelial cells have no receptors on the outer membrane for the uptake of viruses such as hepatitis C, herpes, adeno-and polioviruses. In this way, epithelial cells are effectively protected from disease-causing germs. Still, it manages various viruses, such as to penetrate the human immunodeficiency virus HIV through the mucous membrane in the body. As this penetration takes place at the molecular level, had been an unsolved mystery. They discussed three hypotheses: First, mechanical damage to the mucosa as a cause, secondly, the presence of yet unknown receptors on the cell membrane, or third, the penetration of viruses through a kind of Trojan horse. Now there is a cell biologist at the University of Zurich for the first time been able to identify the mechanism of adenovirus infection.

Adenoviruses (Photo: Michele Gastaldelli, University of Zurich, Institute of Molecular Biology) Red colored adenovirus particles are located on the periphery of a human epithelial cell and move continuously to the cell nucleus at the bottom. Marked in green are the cell belonging to the endosomal vesicles (blisters). Most virus particles do not move together with these endosomes, but together with others, not visible here, molecules of the cell's nucleus to (vertical axis = 11μm).

Verena Lütschg and cell biologists at the Institute of Molecular Biology under the direction of Urs Greber show in the journal Nature recently published online communications, such as adenovirus type 5 in the lung epithelium caused by an infection of the immune response to exploit the further course of infection. Adenoviruses using phagocytes and the onset of production of antiviral cytokines as a door opener for the infection of lung epithelial cells.

Exposure of shielded receptors

Antiviral cytokines play an important role in immunological reactions and lead to inflammatory reactions, for example. They bring to the epithelial cells, some in their exposure under normal circumstances, and thus shielded receptors to activate immune cells for defense. For healthy people with an infection of the lungs from adenovirus type 5 is harmless, since they cause only a cold. Under great stress situations or in chronic respiratory diseases, adenoviruses cause acute infections but strong, which can be lethal under certain circumstances.

The newly identified infectious mechanism may serve as a model for which way to penetrate into the Schleimhautepithelzellen and pathogens enter the body. He is also particularly with regard to therapeutic applications of great importance. Already today, adenovirus type 5 very often as a delivery vehicle for cancer gene therapy used. The knowledge of the transportation route will serve to drive this gene therapies, but also the development of specifically acting anti-cancer drugs, continued.

Literature:

Verena Lütschg, Karin Boucke, Silvio Hemmi, Urs F. Greber, Chemotactic antiviral cytokines promote apical entry of infectious human adenovirus into polarized epithelial cells, Nature Communications DOI: 10.1038/ncomms1391.

Source: University of Zurich