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Human Cytomegalovirus UL131-128 Genes Are Indispensable for Virus Growth in Endothelial Cells and Virus Transfer to Leukocytes

2004; American Society for Microbiology; Volume: 78; Issue: 18 Linguagem: Inglês

10.1128/jvi.78.18.10023-10033.2004

1098-5514

Gabriele Hahn, Maria Grazia Revello, Marco Patrone, Elena Percivalle, Giulia Campanini, Antonella Sarasini, Markus Wagner, Andrea Gallina, Gabriele Milanesi, Ulrich H. Koszinowski, Fausto Baldanti, Giuseppe Gerna,

Neutrophil, Myeloperoxidase and Oxidative Mechanisms

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.