Systemic expression of Kaposi sarcoma herpesvirus (KSHV) Vflip in endothelial cells leads to a profound proinflammatory phenotype and myeloid lineage remodeling in vivo.

TitleSystemic expression of Kaposi sarcoma herpesvirus (KSHV) Vflip in endothelial cells leads to a profound proinflammatory phenotype and myeloid lineage remodeling in vivo.
Publication TypeJournal Article
Year of Publication2015
AuthorsBallon G, Akar G, Cesarman E
JournalPLoS Pathog
Volume11
Issue1
Paginatione1004581
Date Published2015 Jan
ISSN1553-7374
KeywordsAnimals, Cell Lineage, Cellular Microenvironment, Endothelial Cells, Inflammation, Inflammation Mediators, Mice, Mice, Inbred C57BL, Mice, Inbred CBA, Mice, Transgenic, Myeloid Cells, Phenotype, Sarcoma, Kaposi, Viral Proteins
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.

DOI10.1371/journal.ppat.1004581
Alternate JournalPLoS Pathog
PubMed ID25607954
PubMed Central IDPMC4301867
Grant ListR01 CA103646 / CA / NCI NIH HHS / United States
R01CA103646 / CA / NCI NIH HHS / United States
Related Lab: 
Related Faculty: 
Ethel Cesarman, M.D., Ph.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700