Alphaherpesviruses have developed a sophisticated and fine-tuned balance with the immune system. Disturbance of this balance can result in aggravated alphaherpesvirus disease. For example, deficiencies in the type I interferon (IFN-I) response are associated with life-threatening encephalitis caused by herpes simplex virus (HSV).
IFN-I are the strongest antiviral molecules produced by the innate immune response. Plasmacytoid dendritic cells (pDC) are the most powerful producers of IFN-I.
Recent work at the laboratory, including work by the FWO mandate holder, has led to exciting new leads in this field, including the identification of two conserved alphaherpesvirus proteins (US3 and gB) that modulate the ability of pDC to produce IFN-I. The main goal of the current project is therefore to unravel how these viral proteins modulate pDC activity.
Apart from their importance as very successful pathogens, alphaherpesviruses are central in a very exciting recent field of research: oncolytic virotherapy, where viruses like HSV are used to fight cancer. One of the critical elements in this field is optimizing the interaction between the oncolytic viral vector and the host immune system, including pDC. Building further on an existing collaboration with Prof. Chiocca of Harvard University, a world expert in the field of HSV oncolytic vectors, the information generated in the current project will be used to design oncolytic HSV vectors with an optimized ability to trigger pDC.