title: Systemic expression of Kaposi sarcoma herpesvirus (KSHV) Vflip in endothelial cells leads to a profound proinflammatory phenotype and myeloid lineage remodeling in vivo.
abstract: KSHV is the causative agent of Kaposi sarcoma (KS), a spindle-shaped endothelial cell neoplasm accompanied by an inflammatory infiltrate. To evaluate the role of KSHV vFLIP in the pathogenesis of KS, we constructed mice with inducible expression of vFLIP in endothelial cells. Abnormal cells with endothelial marker expression and fusiform appearance were observed in several tissues reminiscent of the spindle cells found in KS. Serum cytokines displayed a profound perturbation similar to that described in KSHV inflammatory cytokine syndrome (KICS), a recently described clinical condition characterized by elevated IL6 and IL10. An increased myeloid component with suppressive immune phenotype was found, which may contribute to functional changes in the microenvironment and cellular heterogeneity as observed in KS. These mice represent the first in vivo demonstration that vFLIP is capable of inducing vascular abnormalities and changes in host microenvironment with important implications for understanding the pathogenesis and treating KSHV-associated diseases.
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Gianna
authors.initials: G
authors.lastname: Ballon
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Gunkut
authors.initials: G
authors.lastname: Akar
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York, United States of America.
authors.forename: Ethel
authors.initials: E
authors.lastname: Cesarman
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000235:genetics; D060833:Cellular Microenvironment / Q000235:genetics / Q000276:immunology; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000502:physiology*; D010641:Phenotype; D012514:Sarcoma, Kaposi / Q000821:virology; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D014764:Viral Proteins; C481275:viral FLIP protein, Human herpesvirus 8