Human cytomegalovirus UL131-128 genes are indispensable for virus growth in endothelial cells and virus transfer to leukocytes

J Virol. 2004 Sep;78(18):10023-33. doi: 10.1128/JVI.78.18.10023-10033.2004.

Abstract

Human cytomegalovirus (HCMV), a ubiquitous human pathogen, is the leading cause of birth defects and morbidity in immunocompromised patients and a potential trigger for vascular disease. HCMV replicates in vascular endothelial cells and drives leukocyte-mediated viral dissemination through close endothelium- leukocyte interaction. However, the genetic basis of HCMV growth in endothelial cells and transfer to leukocytes is unknown. We show here that the UL131-128 gene locus of HCMV is indispensable for both productive infection of endothelial cells and transmission to leukocytes. The experimental evidence for this is based on both the loss-of-function phenotype in knockout mutants and natural variants and the gain-of-function phenotype by trans-complementation with individual UL131, UL130, and UL128 genes. Our findings suggest that a common mechanism of virus transfer may be involved in both endothelial cell tropism and leukocyte transfer and shed light on a crucial step in the pathogenesis of HCMV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cells, Cultured
  • Chromosomes, Artificial, Bacterial / genetics
  • Cytomegalovirus / genetics*
  • Cytomegalovirus / growth & development*
  • Cytomegalovirus / isolation & purification
  • Cytomegalovirus / pathogenicity
  • Cytomegalovirus Infections / etiology
  • Cytomegalovirus Infections / virology
  • Endothelium, Vascular / virology
  • Genes, Viral*
  • Genetic Complementation Test
  • Humans
  • Leukocytes / virology
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Sequence Homology, Amino Acid
  • Virulence / genetics