Alphaherpesviruses have developed a finetuned balance with the immune system of the host,
allowing (lifelong) infection of the host and efficient transmission but at the same time leading to
relatively benign symptoms, such as cold sores with herpes simplex virus 1 (HSV-1).
Disturbance of the balance with the immune system can have severe consequences. Deficiencies in
Natural Killer (NK) cells severely affect the balance, and can lead to life-threatening disease, such as
HSV-1 encephalitis (1, 2).
NK cells have an array of activating and inhibitory receptors on their cell surface. When an NK cell
encounters a potential target cell, it is the balance of activating and inhibitory signals elicited via
these receptors that determines whether the NK cell will kill the cell. Despite the obvious critical
role of NK cells in alphaherpesvirus pathogenesis, very little is known on the activating and
inhibitory signals received by NK cells when encountering an alphaherpesvirus-infected cell.
Recent, exciting data of the promoters show that particular alphaherpesvirus proteins elicit
inhibitory (gD, US3) or activating (gB) signals to NK cells. The general aim of the current project is to
unravel the mechanism how these viral proteins affect NK cell activity. The fundamental knowledge
generated can have important consequences for the design of alphaherpesvirus-based vaccines and