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Mutational mapping of pUL131A of human cytomegalovirus emphasizes its central role for endothelial cell tropism.
Schuessler, Andrea; Sampaio, Kerstin Laib; Straschewski, Sarah; Sinzger, Christian.
  • Schuessler A; Institute of Medical Virology and Epidemiology of Virus Diseases, University of Tuebingen, Tuebingen, Germany.
J Virol ; 86(1): 504-12, 2012 Jan.
Article en En | MEDLINE | ID: mdl-22031943
ABSTRACT
The UL131A protein is part of a pentameric variant of the gcIII complex in the virion envelope of human cytomegalovirus (HCMV), which has been found essential for efficient entry into endothelial cells (ECs). Using a systematic mutational scanning approach, we aimed to define peptide motifs within the UL131A protein that contribute to EC infection. Mutant viruses were generated in which charged amino acids within frames of 2 to 6 amino acids were replaced with alanines. The resulting viruses were evaluated with regard to their potential to infect EC cultures. Four clusters of charged amino acids essential for EC infection were identified (amino acids 22 to 27, 32 to 35, 64 to 69, and 116 to 121). Mutations of individual charge clusters within amino acids 72 to 104 caused minor reductions of EC tropism, but these effects were additive in a combined mutation, showing that this region also contributes to EC tropism. Only charge clusters within amino acids 46 to 58 were found irrelevant for EC infection. In conclusion, the unusual sensitivity to mutations, together with the remarkable conservation of the UL131A protein, emphasizes its particular role for EC tropism of HCMV.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Proteínas del Envoltorio Viral / Infecciones por Citomegalovirus / Citomegalovirus / Células Endoteliales / Tropismo Viral / Mutación Límite: Humans Idioma: En Año: 2012 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Proteínas del Envoltorio Viral / Infecciones por Citomegalovirus / Citomegalovirus / Células Endoteliales / Tropismo Viral / Mutación Límite: Humans Idioma: En Año: 2012 Tipo del documento: Article