The development of medications like antibiotics has fostered the assumption that modern medicine will, in due time, provide the means to solve all problems of infectious diseases. However, infection is still one leading cause of morbidity and mortality throughout the world. The reasons for this apparent failure in the infection-control are multifarious. Pathogens that appeared to be close to control, like tuberculosis or staphylococcus bacteria revived due to resistances, which developed during antimicrobial chemotherapy with antibiotics. Immunosuppressing pathogens like HIV pave the way for opportunistic secondary infections. Zoonotic viruses like those causing influenza, Dengue fever, or SARS, travel and increased human mobility may lead to widely unlimited spread of infectious diseases with consequences that may well be beyond our conception. Additionally, medical progress like transplantation of stem cells for cancer therapy gave rise to clinical settings, where patients may be highly susceptible to opportunistic infections, e.g. with fungi or herpesviruses.
Latent or persistent viral infections are accompanied by the interplay between the hosts antiviral defence and the mechanisms of the virus to evade these control strategies. The understanding of this interplay and the resulting pathogenesis is crucial for the development of antiviral therapeutics and vaccines. Long term co-evolution of particular viruses and host led to the evolvement of complex herpesviruses, like the cytomegaloviruses, which developed multiple levels of interference with their human host. Studying the molecular events underlying virus-host interactions provides insight into the molecular biology of human cytomegalovirus (HCMV). Based on this, novel strategies for the development of antiviral agents and vaccines can be designed.
The HCMV, a ß-herpesvirus, is characterized by its strict host specificity. Since the beginning of the 20th century, HCMV is widely appreciated as a cause of congenital disease and childhood sequelae. Survivors suffer from central nervous system disorders, sensorineural hearing loss and visual impairment. Besides that, HCMV infection or reactivation is a serious and life-threatening complication of hematopoietic stem cell or solid organ transplantation and is still an issue in HIV-infected individuals despite the availability of effective anti-retroviral agents.
HCMV has a linear double stranded DNA genome of high complexity and a coding capacity of over 150 different genes. With that it is one of the most complex of all known human viruses. Since the viral genome has become accessible to site-directed mutagenesis, the function of particular viral genes can be analyzed.
The main interest of our group is the analysis of virus-host interactions with particular focus on host defence mechanisms. Moreover, the development of prophylactic strategies for the prevention of HCMV infection and disease is a major goal. Here, subviral particles, so called Dense Bodies (DBs) have been identified as a promising vaccine candidate, which up to now is ready for first-in-man clinical evaluation.
- Analysis of virus-host interaction with particular emphasis on innate host defense mechanisms
- Intracellular transport of viral proteins and particle assembly
- Development of subviral Dense Bodies as a vaccine candidate against HCMV infection
- Design of phase I clinical studies to investigate the tolerability of Dense Bodies in human
- Development of Dense Bodies as a safe HCMV vaccine
- Impact of Dense Bodies on host cells and HCMV replication
- Role of HCMV tegument proteins in viral replcation and particle assembly