• Media type: E-Article
  • Title: Mutational Mapping of UL130 of Human Cytomegalovirus Defines Peptide Motifs within the C-Terminal Third as Essential for Endothelial Cell Infection
  • Contributor: Schuessler, Andrea; Sampaio, Kerstin Laib; Scrivano, Laura; Sinzger, Christian
  • Published: American Society for Microbiology, 2010
  • Published in: Journal of Virology, 84 (2010) 18, Seite 9019-9026
  • Language: English
  • DOI: 10.1128/jvi.00572-10
  • ISSN: 0022-538X; 1098-5514
  • Origination:
  • Footnote:
  • Description: ABSTRACT The UL130 gene is one of the major determinants of endothelial cell (EC) tropism of human cytomegalovirus (HCMV). In order to define functionally important peptides within this protein, we have performed a charge-cluster-to-alanine (CCTA) mutational scanning of UL130 in the genetic background of a bacterial artificial chromosome-cloned endotheliotropic HCMV strain. A total of 10 charge clusters were defined, and in each of them two or three charged amino acids were replaced with alanines. While the six N-terminal clusters were phenotypically irrelevant, mutation of the four C-terminal clusters each caused a reduction of EC tropism. The importance of this protein domain was further emphasized by the fact that the C-terminal pentapeptide PNLIV was essential for infection of ECs, and the cell tropism could not be rescued by a scrambled version of this sequence. We conclude that the C terminus of the UL130 protein serves an important function for infection of ECs by HCMV. This makes UL130 a promising molecular target for antiviral strategies, e.g., the development of antiviral peptides.
  • Access State: Open Access