Human cytomegalovirus UL131-128 genes are indispensable for virus growth in endothelial cells and virus transfer to leukocytes.
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.
Hahn
Gabriele
G
Max von Pettenkofer Institut, Abteilung Virologie, Ludwig-Maximilians-Universität München, Munich, Germany. ghahn@m3401.mpk.med.uni-muenchen.de
Revello
Maria Grazia
MG
Patrone
Marco
M
Percivalle
Elena
E
Campanini
Giulia
G
Sarasini
Antonella
A
Wagner
Markus
M
Gallina
Andrea
A
Milanesi
Gabriele
G
Koszinowski
Ulrich
U
Baldanti
Fausto
F
Gerna
Giuseppe
G
D000595:Amino Acid Sequence; D002478:Cells, Cultured; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D003587:Cytomegalovirus / Q000235:genetics* / Q000254:growth & development* / Q000302:isolation & purification / Q000472:pathogenicity; D003586:Cytomegalovirus Infections / Q000209:etiology / Q000821:virology; D004730:Endothelium, Vascular / Q000821:virology; D005814:Genes, Viral; D005816:Genetic Complementation Test; D006801:Humans; D007962:Leukocytes / Q000821:virology; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017386:Sequence Homology, Amino Acid; D014774:Virulence / Q000235:genetics