An unknown inhibitory mechanism is found for human cytomegalovirus


Especially in view, the researchers have the first step of viral infection and they are complicated. "A group of our immune cells, macrophages, respond with a strong interferon response to the virus and initiate defense against HCMV. However, receptors that allow macrophages to see viruses reside in immune cells. So long as macrophages are not directly infected by HCMV, they don't recognize its existence, "said the scientist at the Institute for Experimental Infection Research. Jennifer Becker. However, the first cells that infect HCMV are not immune cells, but epithelial and endothelial cells in the nose, mouth and blood vessels.
To understand what actually happened with HCMV infection, Jennifer Becker has conducted a series of experiments with human cells: first, she has infected epithelial cells with viruses and added macrophages for 24 hours to these infected cells. The results are as expected: macrophages do not produce interferon, because without a virus free, there is no macrophage infection that occurs, and thus the virus remains invisible to receptors in macrophages, which start interferon production. "However, if we infect macrophages directly with viruses, they respond as we expect from immune cells and release interferon, the messenger who announces virus attacks and keeps the virus from attacking."
Researchers know that human cytomegalovirus requires three days for the reproductive cycle. So in another experiment, they infected epithelial cells with HCMV and cultured these infected cells along with healthy macrophages for several days. "From now on, that will be mysterious," said Jennifer Becker, "because in the culture with infected epithelial cells and macrophages, we observed that the virus was severely inhibited. Even after several days of cultivation, we did not see any infection in the macrophages, no free interferon and even some viruses. "Something – it's not interferon – inhibits viruses and protects macrophages. In addition, researchers have observed that for this protection, infected epithelial cells and macrophages must be spatially close to each other. If the distance between cells becomes too large, the escape does not work anymore. Do macrophages or epithelial cells produce this mysterious factor? Not known. The only certainty is that both cells are needed for this. "This mysterious factor inhibits the spread of the virus over a longer period of time. In its search, we investigated known mechanisms and messengers, but interferon or other classic antiviral factors are not associated with this effect," said Jennifer Becker.
Now the TWINCORE team is making a breakthrough and using the most advanced technology, they will trace this mysterious factor, "because it might hide behind a completely new antivirus mechanism, which gives us a new perspective for virus inhibition," the director closed Prof. Ulrich Kalinke.

Becker J, Kinast V, Döring M, Lipps C, Duran V, J Spain, Tegtmeyer PK, Wirth D, L Cicin-Sain, Alcami A, Kalinke U. (2018) Human-derived monocyte macrophages inhibit HCMV independent of classic cytokines antivirus .Virulence. 2018; 9 (1): 1669-1684.

scientific contact:
Dr. Jennifer Becker, jennifer.becker (at)
Tel: +49 (0) 511 220027-163

Original publication:
doi: 10.1080 / 21505594.2018.1535785.

idw 2018/11


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