Die Rolle von UL128-131-abhängigen Endozytosemechanismen für den Endothelzelltropismus des menschlichen Cytomegalovirus (HCMV)

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This project is based on the hypothesis that interactions of tegument or capsid proteins of human cytomegalovirus (HCMV) with cellular proteins of the dynein/dynactin complex are critical for cell tropism differences between endotheliotropic HCMV/E strains and nonendotheliotropic HCMV/F strains. We will (1) analyze the contribution of various viral structural proteins to EC tropism by the construction of HCMV/F viruses pseudotyped with the respective HCMV/E proteins, (2) combine single virion immunofluorescence staining with differential removal of cytoskeleton components to dissect the role of actin and microtubules during viral penetration, transport towards the MTOC and delivery to the nucleus, and (3) analyze events of binding and phosphorylation/dephosphorylation between viral and cellular structural proteins by a combination of differential precipitation with 2-D gel electrophoresis and protein identification techniques. In conclusion, we expect insight into the molecular mechanisms underlying interstrain differences in the EC tropism of HCMV, with potential implications for the development of new antiviral strategies and the development of EC-targeted vaccines.