The long-term goal of this workgroup is to limit the clinical, epidemiological and economical impact of virus infections by vaccination, treatment with antiviral drugs or with biological response modifiers. The research focuses on acute respiratory virus infections such as influenza viruses, human metapneumovirus (hMPV), respiratory syncytial virus (RSV), measles virus (MV), coronaviruses (CoV), as well as on chronic virus infections such as hepatitis B and C viruses and herpesviruses like herpes simplex virus (HSV), varicella zoster virus (VZV), and simian varicella virus (SVV). Knowledge of the (immuno-) pathogenesis of these virus infections, both in humans and in animals, is the fundamental basis of the work. A special element of this research is to apply the expertise and techniques of several disciplines, including virology, immunology, pathology and genomics in a highly integrated fashion. Studies on the natural and vaccine-induced immune response to these viruses are performed to improve existing and develop novel vaccines and other intervention strategies. Depending on the viral pathogen and what type of cellular and/or humoral immunity is most desired, subunit vaccines, whole inactivated vaccines, live-attenuated vaccines and vectored vaccines are studied. Vaccine candidates are developed using both classical and state-of-the-art techniques in biochemistry and molecular biology. Humoral and cellular immunological parameters are monitored, with special emphasis on correlates of protection and vaccine-induced immune-pathogenesis for selected viral pathogens. In addition the efficacy of novel and existing antiviral treatments and the emergence of drug-resistant virus variants are monitored in order to improve antiviral treatment regimens. Our high quality molecular diagnostics unit forms an important bridge between clinic and research. The efficacy of antiviral drugs to combat AIDS (HIV-1 and HIV-2), influenza, hepatitis (hepatitis B and C viruses) and herpes (HSV and VZV) is measured in relation to drug-resistance, host and epidemiological parameters. An important element of the research of this workgroup is also related to studies of wild animal reservoirs of emerging viral infections: both virus discovery and studies on the epidemiology and pathology of potential emerging pathogens in wild animals are persued. The discovery of novel viruses associated with human diseases is included in this workgroup since the etiology of many human and animal diseases is still unknown; the early identification of novel viral pathogens will allow the timely development of intervention strategies using surveillance tools, vaccines, antiviral compounds and other medicines to limit their impact. It is well appreciated that interspecies transmission of pathogens may result in the emergence of new infectious diseases in humans and animals. By comparing and contrasting emerging pathogens with those of closely related pathogens in more or less related host species, the various host genomic pathways are delineated thus determining the outcome of zoonotic transmission and adaptation to the newly invaded species. It is anticipated that the outcome of this research will improve our preparedness to combat newly emerging viruses.