Inhibition of replication of the human cytomegalovirus through interaction with tropism-relevant envelope protein

• Applicant: Professor Dr. Christian Sinzger
• Subject Area: Virology
• Term: from 2013 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 230446674

About 50 % of the population is infected with the human cytomegalovirus (HCMV). Following infection the virus establishes lifelong persistence in the organism without clinical symptoms. Immunosuppression can lead to reactivation, hematogenous dissemination and eventually organ manifestation of the virus with severe morbidity particularly in lung and gastrointestinal tract. The infection of vascular endothelial cells (ECs) and blood cells depends mainly on the viral genes UL128, UL130 and UL131A. We have recently mapped these genes by a systematic mutational approach with regard to functionally important charged peptide clusters. Based on this information we now aim at (i) revealing the molecular mechanisms underlying EC infection, (ii) development of candidate vaccine strains that are attenuated regarding EC infection and (iii) targeted development of inhibitory peptides with the potential to prevent hematogenous dissemination of HCMV. First we will analyze how the various mutations affect the protein composition of the viral envelope, virion attachment to ECs and fusion of viral envelope with cellular membranes. Mutations that reduce EC tropism but maintain the protein composition of the virus envelope will be combined for vaccine development. Peptides with impact on the interaction within the UL128-131A containing envelope protein complex will be further evaluated regarding suitability as potential antiviral drugs.

• DFG Programme: Research Grants