Human Cytomegalovirus (HCMV) Reveals Position of Bistability in Receptor Expression of Natural Killer Cells.
Thomas Holst-Hansen, NBI



Natural killer (NK) cells are part of the innate immune system. Contrary to the adaptive immune system, NK cells provide a non-specific protection, especially useful in the fight against tumor-formation and viral diseases. A combination of inhibiting and activating receptors at the surface of the cells, react to imbalances in naturally occurring surface proteins of other cells, and initiate a killing process. These imbalances are typically observed in stressed or infected cells.

Human Cytomegalovirus (HCMV) is a common herpesvirus with an estimated level of infected ranging between 60 and 70% of the population in industrialized countries and even higher in developing countries. After infection, the virus is latent within the host, and can be reactivated but never entirely removed from the system. Remarkably, HCMV changes the receptor repertoire of the hosts NK cells - an effect that to my knowledge is not observed in response to other viral infections. In HCMV positive donors, a particular subset of the NK population that expresses the receptor NKG2C expands, and the average NKG2C receptor concentration among expressing cells increases. Furthermore the population of killer cells will express a bistable distribution of the receptor; a single cell either has the receptor or not.

In this talk I will present the work I did in the group of Jordi Garcia-Ojalvo (UPF, Barcelona). Using data from HCMV infected donors, I show that gene copy numbers can reveal the position of a bistability to be either upstream or downstream of gene transcription. Further I suggest a possible mechanism for the bistable expression level.

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