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Especially in sight, researchers have the first steps of infection with the virus and they are delicate. "A group of our immune cells, the macrophages, respond with a strong interferon response to the virus and initiate a defense against HCMV.However, the receptors that allow macrophages to detect the virus are inside the immune cells. So, as long as macrophages are not directly infected with HCMV, they do not recognize its presence, "says the scientist of the Institute for Experimental Research on Infections. Jennifer Becker. However, the first cells that infect HCMV are not the immune cells, but the epithelial and endothelial cells of the nose, mouth and blood vessels.
In order to understand what is really happening with HCMV infection, Jennifer Becker performed a series of experiments on human cells: she first infected the epithelial cells with the virus and added macrophages for 24 hours to these infected cells. The result was as expected: the macrophages did not produce interferon because without a free virus, no infection of the macrophages occurred and the viruses thus remained invisible to the receptor in the macrophages, which initiated the production of 39; interferon. "However, if we directly infect macrophages with the virus, they react as one would expect from immune cells and release interferon, the messenger that heralds the virus's attack and holds it from a distance. "
Researchers know that human cytomegaloviruses require three days for a reproductive cycle. Thus, in another experiment, they infected the epithelial cells with HCMV and cultured them with healthy macrophages for several days. "From now on, it will be mysterious," explains Jennifer Becker, "because in the shared culture of infected epithelial cells and macrophages, we observe that the virus is strongly inhibited, even after several days of culture we do not see any infection. macrophages, no interferon and even some free viruses. "Something – it's not interferon – inhibits the virus and protects macrophages. In addition, the researchers observed that for this protection, the infected epithelial cells and macrophages had to be close to each other in space. If the distance between cells becomes too large, the exhaust will no longer work. Do macrophages or epithelial cells produce this mysterious factor? Unknown. The only certainty is that both cells are needed for this. "This mysterious factor inhibits the spread of the virus over a long period of time.We researched the known mechanisms and messengers, but neither interferon nor other clbadical antiviral factors are related to this effect. "says Jennifer Becker.
Now the TWINCORE team is innovating and using the most advanced technologies to detect this mysterious factor, "because it may be hiding behind a completely new antiviral mechanism, which offers us a new perspective for inhibiting viruses," concludes the director, Prof. Ulrich Kalinke.
publication:
Becker J, Kinast V, Döring M, C Lipps, Duran V, Spanish J, Tegtmeyer PK, Wirth D, Cicin-Sain L, Alcami A and Kalinke U. (2018) Macrophages derived from human monocytes inhibiting HCMV independent of clbadical antiviral cytokines.Virulence. 2018; 9 (1): 1669-1684.
scientific contact:
Dr. Jennifer Becker, jennifer.becker (at) twincore.de
Tel: +49 (0) 511 220027-163
Original publication:
doi: 10.1080 / 21505594.2018.1535785.
idw 2018/11
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