Activation of NF-kappaB by the latent vFLIP gene of Kaposi's sarcoma-associated herpesvirus is required for the spindle shape of virus-infected endothelial cells and contributes to their proinflammatory phenotype.
Kaposi's sarcoma (KS) is an inflammatory angioproliferative lesion induced by the infection of endothelial cells with the KS-associated herpesvirus (KSHV). Infected endothelial cells assume an elongated (spindle) shape that is one of the histologic signatures of KS. In vitro, latent viral infection of primary endothelial cells (but no other cell type) strikingly recapitulates these morphological findings. Here we report that the spindling phenotype involves major rearrangement of the actin cytoskeleton and can be attributed to the expression of a single viral protein, vFLIP, a known activator of NF-kappaB. Consistent with this, the inhibition of NF-kappaB activation blocks vFLIP-induced spindling in cultured endothelial cells. vFLIP expression in spindle cells also induces the production of a variety of proinflammatory cytokines and cell surface adhesion proteins that likely contribute to the inflammatory component of KS lesions.
Grossmann
Claudia
C
Howard Hughes Medical Institute and Department of Microbiology, University of California Medical Center, San Francisco, 94143, USA.
Podgrabinska
Simona
S
Skobe
Mihaela
M
Ganem
Don
D
D000199:Actins / Q000378:metabolism; D002448:Cell Adhesion; D048430:Cell Shape; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism* / Q000821:virology; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D019288:Herpesvirus 8, Human / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000821:virology; D016328:NF-kappa B / Q000378:metabolism*; D010641:Phenotype; D012514:Sarcoma, Kaposi / Q000378:metabolism* / Q000821:virology; D014764:Viral Proteins / Q000378:metabolism*; D017735:Virus Latency / Q000502:physiology
D000199:Actins; D016207:Cytokines; D016328:NF-kappa B; D014764:Viral Proteins; C481275:viral FLIP protein, Human herpesvirus 8