Keeping herpes viruses dormant
Dendritic cells play an important role in the inhibition of cytomegaloviruses
The cytomegalovirus (CMV) is a herpes virus that is present, but undetected, in the majority of the human population. It causes symptoms only once the immune system of the host becomes weakened. But then it can even be fatal. For this reason, researchers are looking for methods to keep the virus in its sleeping phase, also called latency. According to a current study conducted by scientists of the Helmholtz Centre for Infection Research (HZI), specific cells of the immune system, the so-called dendritic cells, play a crucial, and thus far unknown, role in the inhibition of Viruses. The researchers published their results in the "Journal of Virology".
Almost every human has herpes viruses in his or her body, but the Viruses, including the cytomegalovirus, usually persist in the body in an inactive form. Once the virus becomes active in humans with a weakened immune system, it can lead to serious diseases and, in the worst case, fatality. "This is why it is so important to keep the virus in its latency phase and to prevent it from becoming harmful," says Prof Luka Cicin-Sain, who is the director of the "Immune Aging and Chronic Infections" junior research group at the HZI.
Dendritic cells may play a more important role in the inhibition of viruses than was previously known. From what we know to date, the cells are mostly thought to have a function in the recognition of intruding pathogens. They then relay this information to so-called T-cells and thus initiate the immune response. "We just showed for the first time that they can have an antiviral effect by themselves and in the absence of T-cells and inhibit CMV , " says Julia Holzki, who is a PhD student in this research group and the lead author of the study.
This interaction between immune cells and CMV-infected cells was studied by the researchers in a so-called co-culture system. Infected cells and dendritic cells were cultured jointly either with or without T-cells. Only T-cells were added to the infected cells in the control experiment. "T-cells alone had no inhibitory effect on the virus. Dendritic cells have this effect, and they even have this effect if there were added after the Infection," says Holzki. But the cells only effect an inhibition of the virus without killing it. The virus became active again once the dendritic cells lost contact to the infected cells.
It was also evident that the dendritic cells have an antiviral effect on cells only if these possess interferon receptors. Interferons are messenger substances of the immune system that are produced in cells after viral infections and can prevent the Viruses from multiplying inside the cells. "The results indicate that Interferons are the key to the antiviral effect of dendritic cells and to the inhibition of cytomegaloviruses," says Cicin-Sain. "However, some other factors seem to be involved as well, which now need to be identified."
If this is successful, it may be feasible in the future to use dendritic cells to keep cytomegaloviruses dormant. "In addition, we are testing whether or not dendritic cells can assume similar functions with respect to other Viruses as well," says Holzki.
Julia Katharina Holzki, Franziska Dağ, Iryna Dekhtiarenko, Ulfert Rand, Rosaely Casalegno-Garduño, Stephanie Trittel, Tobias May, Peggy Riese and Luka Čičin-Šain.Type I IFN released by Myeloid Dendritic Cells reversibly impairs Cytomegalovirus replication by inhibiting immediate early gene expression. J. Virol. 2015 Jul 22. DOI: 10.1128/JVI.01459-15.