Kurzfassung

Prenatal infection with human cytomegalovirus (HCMV) is one of the most frequent reasons for death or severe congenital disabilities in newborns and infants in developed countries. Neurological deficits, sensorineural hearing loss and visual impairments are among the severe manifestations of the disease, once denominated cytomegalic inclusion disease (CID). Aside from this, HCMV reactivation is a relevant and life-threatening complication of hematopoietic stem cell and solid organ...Prenatal infection with human cytomegalovirus (HCMV) is one of the most frequent reasons for death or severe congenital disabilities in newborns and infants in developed countries. Neurological deficits, sensorineural hearing loss and visual impairments are among the severe manifestations of the disease, once denominated cytomegalic inclusion disease (CID). Aside from this, HCMV reactivation is a relevant and life-threatening complication of hematopoietic stem cell and solid organ transplantation. Antiviral compounds are of some value in the treatment of the latter manifestations, yet they are associated with severe side effects. Such medication, however, is of limited use for the attenuation of the consequences of CID.
The development of a vaccine against HCMV has gained a top-priority status in biomedical research. A promising candidate vaccine, developed in our laboratory, is based on non-infectious, subviral particles of HCMV, termed Dense Bodies (DBs).  These DBs are released by infected culture fibroblasts and can be purified from cell culture supernatants by standard gradient centrifugation technologies. The extraordinary immunogenicity of DBs was demonstrated in the past by our group and this was subject of several, well-acknowledged publications from our institution.  Yet the molecular mechanisms that lead to the formation of DBs in HCMV-infected cells are widely unclear. This project focusses on the definition of those viral proteins that are necessary and sufficient for the formation of DBs. Based on this knowledge, it will be possible to design a viral strain by recombinant technologies that has lost its virulence for humans and thus allows the save production of a DB-based vaccine. Pursuing such a strategy is mandatory to meet the current regulations of vaccine licensing by federal regulatory bodies. This study will concomitantly provide fundamental knowledge about the molecular mechanisms that are operative in the processes of tegumentation, envelopment and release of HCMV particles during permissive infection.» weiterlesen» einklappen