Productive infection of HUVEC by HHV-8 is associated with changes compatible with angiogenic transformations.
Kaposi's Sarcoma (KS) is an angioproliferative disease associated with human herpesvirus 8 (HHV-8) infection. We have characterized the morphologic and phenotypic modifications of HUVEC in a model of productive HHV-8 infection. HHV-8 replication was associated with ultra-structural changes, flattened soma and a loss of marginal folds and intercellular contacts, and morphologic features, spindle cell conversion and cordon-like structures formation. Phenotypic changes observed on cordon-like structures included partial loss and redistribution of CD31/PECAM-1 and VE-cadherin, uPAR up-regulation and de novo expression of CD13/APN. Such changes demonstrate the induction, in HUVEC, of an angiogenic profile. Most of these findings are directly linked to HHV-8-encoded proteins expression, suggesting that HHV-8 itself may participate to the initial steps of the angiogenic transformation in KS.
Foglieni
C
C
Unit of Human Virology, Department of Biological and Technological Research (DIBIT), Medicine University of Milan, Italy.
Scabini
S
S
Belloni
D
D
Broccolo
F
F
Lusso
P
P
Malnati
M S
MS
Ferrero
E
E
D000956:Antigens, Viral / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000648:ultrastructure / Q000821:virology*; D015967:Gene Expression Regulation, Viral; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology*
D000956:Antigens, Viral; D015850:Interleukin-6; C404106:MRC2 protein, human; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D011956:Receptors, Cell Surface; D014764:Viral Proteins; C109540:latency-associated nuclear antigen