U94 of human herpesvirus 6 inhibits in vitro angiogenesis and lymphangiogenesis.
Human herpesvirus 6 (HHV-6) is a lymphotropic virus, but recent observations showed that also vascular endothelial cells (ECs) are susceptible to infection, both in vivo and in vitro. The observation that lymph nodes are a site of viral persistence suggests that lymphatic ECs (LECs) might be even more relevant for HHV-6 biology than vascular ECs. Here, we provide evidence that HHV-6 can infect LECs in vitro and establish a latent infection. Thus HHV-6 infection induces the loss of angiogenic properties both in LECs and in vascular ECs, as shown by the inability to form capillary-like structures and to seal wound scratches. The antiangiogenic effects observed in infected cells are associated to the expression of HHV-6 U94/rep, a latency-associated gene. In fact, transfection of U94/rep or addition of recombinant U94/REP protein to ECs inhibits the formation of in vitro capillary-like structures, reduces migration of ECs, and blocks angiogenesis, rendering rat aortic rings insensitive to VEGF-induced vasculogenetic activity. The ability of U94/rep to block different angiogenetic steps may lead to approaches in the potential control of the proliferation of blood and lymphatic vessels.
Caruso
Arnaldo
A
Section of Microbiology, University of Brescia, Piazzale Spedali Civili 1, 25123 Brescia, Italy.
Caselli
Elisabetta
E
Fiorentini
Simona
S
Rotola
Antonella
A
Prandini
Alberto
A
Garrafa
Emirena
E
Saba
Elisa
E
Alessandri
Giulio
G
Cassai
Enzo
E
Di Luca
Dario
D
D020533:Angiogenesis Inhibitors / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D042783:Endothelial Cells / Q000502:physiology / Q000821:virology*; D004797:Enzyme-Linked Immunosorbent Assay; D019085:Fluorescent Antibody Technique, Direct; D015654:Herpesvirus 6, Human / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D042583:Lymphangiogenesis / Q000502:physiology*; D016133:Polymerase Chain Reaction; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology*
D020533:Angiogenesis Inhibitors; D017931:DNA Primers; D014764:Viral Proteins